Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4183C>T (p.Gln1395Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Apr 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4183C>T (p.Gln1395Ter)
Variation ID: 55125 Accession: VCV000055125.56
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43090946 (GRCh38) [ NCBI UCSC ] 17: 41242963 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Oct 20, 2024 Apr 22, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4183C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln1395Ter nonsense NM_001407571.1:c.3970C>T NP_001394500.1:p.Gln1324Ter nonsense NM_001407581.1:c.4183C>T NP_001394510.1:p.Gln1395Ter nonsense NM_001407582.1:c.4183C>T NP_001394511.1:p.Gln1395Ter nonsense NM_001407583.1:c.4183C>T NP_001394512.1:p.Gln1395Ter nonsense NM_001407585.1:c.4183C>T NP_001394514.1:p.Gln1395Ter nonsense NM_001407587.1:c.4180C>T NP_001394516.1:p.Gln1394Ter nonsense NM_001407590.1:c.4180C>T NP_001394519.1:p.Gln1394Ter nonsense NM_001407591.1:c.4180C>T NP_001394520.1:p.Gln1394Ter nonsense NM_001407593.1:c.4183C>T NP_001394522.1:p.Gln1395Ter nonsense NM_001407594.1:c.4183C>T NP_001394523.1:p.Gln1395Ter nonsense NM_001407596.1:c.4183C>T NP_001394525.1:p.Gln1395Ter nonsense NM_001407597.1:c.4183C>T NP_001394526.1:p.Gln1395Ter nonsense NM_001407598.1:c.4183C>T NP_001394527.1:p.Gln1395Ter nonsense NM_001407602.1:c.4183C>T NP_001394531.1:p.Gln1395Ter nonsense NM_001407603.1:c.4183C>T NP_001394532.1:p.Gln1395Ter nonsense NM_001407605.1:c.4183C>T NP_001394534.1:p.Gln1395Ter nonsense NM_001407610.1:c.4180C>T NP_001394539.1:p.Gln1394Ter nonsense NM_001407611.1:c.4180C>T NP_001394540.1:p.Gln1394Ter nonsense NM_001407612.1:c.4180C>T NP_001394541.1:p.Gln1394Ter nonsense NM_001407613.1:c.4180C>T NP_001394542.1:p.Gln1394Ter nonsense NM_001407614.1:c.4180C>T NP_001394543.1:p.Gln1394Ter nonsense NM_001407615.1:c.4180C>T NP_001394544.1:p.Gln1394Ter nonsense NM_001407616.1:c.4183C>T NP_001394545.1:p.Gln1395Ter nonsense NM_001407617.1:c.4183C>T NP_001394546.1:p.Gln1395Ter nonsense NM_001407618.1:c.4183C>T NP_001394547.1:p.Gln1395Ter nonsense NM_001407619.1:c.4183C>T NP_001394548.1:p.Gln1395Ter nonsense NM_001407620.1:c.4183C>T NP_001394549.1:p.Gln1395Ter nonsense NM_001407621.1:c.4183C>T NP_001394550.1:p.Gln1395Ter nonsense NM_001407622.1:c.4183C>T NP_001394551.1:p.Gln1395Ter nonsense NM_001407623.1:c.4183C>T NP_001394552.1:p.Gln1395Ter nonsense NM_001407624.1:c.4183C>T NP_001394553.1:p.Gln1395Ter nonsense NM_001407625.1:c.4183C>T NP_001394554.1:p.Gln1395Ter nonsense NM_001407626.1:c.4183C>T NP_001394555.1:p.Gln1395Ter nonsense NM_001407627.1:c.4180C>T NP_001394556.1:p.Gln1394Ter nonsense NM_001407628.1:c.4180C>T NP_001394557.1:p.Gln1394Ter nonsense NM_001407629.1:c.4180C>T NP_001394558.1:p.Gln1394Ter nonsense NM_001407630.1:c.4180C>T NP_001394559.1:p.Gln1394Ter nonsense NM_001407631.1:c.4180C>T NP_001394560.1:p.Gln1394Ter nonsense NM_001407632.1:c.4180C>T NP_001394561.1:p.Gln1394Ter nonsense NM_001407633.1:c.4180C>T NP_001394562.1:p.Gln1394Ter nonsense NM_001407634.1:c.4180C>T NP_001394563.1:p.Gln1394Ter nonsense NM_001407635.1:c.4180C>T NP_001394564.1:p.Gln1394Ter nonsense NM_001407636.1:c.4180C>T NP_001394565.1:p.Gln1394Ter nonsense NM_001407637.1:c.4180C>T NP_001394566.1:p.Gln1394Ter nonsense NM_001407638.1:c.4180C>T NP_001394567.1:p.Gln1394Ter nonsense NM_001407639.1:c.4183C>T NP_001394568.1:p.Gln1395Ter nonsense NM_001407640.1:c.4183C>T NP_001394569.1:p.Gln1395Ter nonsense NM_001407641.1:c.4183C>T NP_001394570.1:p.Gln1395Ter nonsense NM_001407642.1:c.4183C>T NP_001394571.1:p.Gln1395Ter nonsense NM_001407644.1:c.4180C>T NP_001394573.1:p.Gln1394Ter nonsense NM_001407645.1:c.4180C>T NP_001394574.1:p.Gln1394Ter nonsense NM_001407646.1:c.4174C>T NP_001394575.1:p.Gln1392Ter nonsense NM_001407647.1:c.4174C>T NP_001394576.1:p.Gln1392Ter nonsense NM_001407648.1:c.4060C>T NP_001394577.1:p.Gln1354Ter nonsense NM_001407649.1:c.4057C>T NP_001394578.1:p.Gln1353Ter nonsense NM_001407652.1:c.4183C>T NP_001394581.1:p.Gln1395Ter nonsense NM_001407653.1:c.4105C>T NP_001394582.1:p.Gln1369Ter nonsense NM_001407654.1:c.4105C>T NP_001394583.1:p.Gln1369Ter nonsense NM_001407655.1:c.4105C>T NP_001394584.1:p.Gln1369Ter nonsense NM_001407656.1:c.4105C>T NP_001394585.1:p.Gln1369Ter nonsense NM_001407657.1:c.4105C>T NP_001394586.1:p.Gln1369Ter nonsense NM_001407658.1:c.4105C>T NP_001394587.1:p.Gln1369Ter nonsense NM_001407659.1:c.4102C>T NP_001394588.1:p.Gln1368Ter nonsense NM_001407660.1:c.4102C>T NP_001394589.1:p.Gln1368Ter nonsense NM_001407661.1:c.4102C>T NP_001394590.1:p.Gln1368Ter nonsense NM_001407662.1:c.4102C>T NP_001394591.1:p.Gln1368Ter nonsense NM_001407663.1:c.4105C>T NP_001394592.1:p.Gln1369Ter nonsense NM_001407664.1:c.4060C>T NP_001394593.1:p.Gln1354Ter nonsense NM_001407665.1:c.4060C>T NP_001394594.1:p.Gln1354Ter nonsense NM_001407666.1:c.4060C>T NP_001394595.1:p.Gln1354Ter nonsense NM_001407667.1:c.4060C>T NP_001394596.1:p.Gln1354Ter nonsense NM_001407668.1:c.4060C>T NP_001394597.1:p.Gln1354Ter nonsense NM_001407669.1:c.4060C>T NP_001394598.1:p.Gln1354Ter nonsense NM_001407670.1:c.4057C>T NP_001394599.1:p.Gln1353Ter nonsense NM_001407671.1:c.4057C>T NP_001394600.1:p.Gln1353Ter nonsense NM_001407672.1:c.4057C>T NP_001394601.1:p.Gln1353Ter nonsense NM_001407673.1:c.4057C>T NP_001394602.1:p.Gln1353Ter nonsense NM_001407674.1:c.4060C>T NP_001394603.1:p.Gln1354Ter nonsense NM_001407675.1:c.4060C>T NP_001394604.1:p.Gln1354Ter nonsense NM_001407676.1:c.4060C>T NP_001394605.1:p.Gln1354Ter nonsense NM_001407677.1:c.4060C>T NP_001394606.1:p.Gln1354Ter nonsense NM_001407678.1:c.4060C>T NP_001394607.1:p.Gln1354Ter nonsense NM_001407679.1:c.4060C>T NP_001394608.1:p.Gln1354Ter nonsense NM_001407680.1:c.4060C>T NP_001394609.1:p.Gln1354Ter nonsense NM_001407681.1:c.4060C>T NP_001394610.1:p.Gln1354Ter nonsense NM_001407682.1:c.4060C>T NP_001394611.1:p.Gln1354Ter nonsense NM_001407683.1:c.4060C>T NP_001394612.1:p.Gln1354Ter nonsense NM_001407684.1:c.4183C>T NP_001394613.1:p.Gln1395Ter nonsense NM_001407685.1:c.4057C>T NP_001394614.1:p.Gln1353Ter nonsense NM_001407686.1:c.4057C>T NP_001394615.1:p.Gln1353Ter nonsense NM_001407687.1:c.4057C>T NP_001394616.1:p.Gln1353Ter nonsense NM_001407688.1:c.4057C>T NP_001394617.1:p.Gln1353Ter nonsense NM_001407689.1:c.4057C>T NP_001394618.1:p.Gln1353Ter nonsense NM_001407690.1:c.4057C>T NP_001394619.1:p.Gln1353Ter nonsense NM_001407691.1:c.4057C>T NP_001394620.1:p.Gln1353Ter nonsense NM_001407692.1:c.4042C>T NP_001394621.1:p.Gln1348Ter nonsense NM_001407694.1:c.4042C>T NP_001394623.1:p.Gln1348Ter nonsense NM_001407695.1:c.4042C>T NP_001394624.1:p.Gln1348Ter nonsense NM_001407696.1:c.4042C>T NP_001394625.1:p.Gln1348Ter nonsense NM_001407697.1:c.4042C>T NP_001394626.1:p.Gln1348Ter nonsense NM_001407698.1:c.4042C>T NP_001394627.1:p.Gln1348Ter nonsense NM_001407724.1:c.4042C>T NP_001394653.1:p.Gln1348Ter nonsense NM_001407725.1:c.4042C>T NP_001394654.1:p.Gln1348Ter nonsense NM_001407726.1:c.4042C>T NP_001394655.1:p.Gln1348Ter nonsense NM_001407727.1:c.4042C>T NP_001394656.1:p.Gln1348Ter nonsense NM_001407728.1:c.4042C>T NP_001394657.1:p.Gln1348Ter nonsense NM_001407729.1:c.4042C>T NP_001394658.1:p.Gln1348Ter nonsense NM_001407730.1:c.4042C>T NP_001394659.1:p.Gln1348Ter nonsense NM_001407731.1:c.4042C>T NP_001394660.1:p.Gln1348Ter nonsense NM_001407732.1:c.4042C>T NP_001394661.1:p.Gln1348Ter nonsense NM_001407733.1:c.4042C>T NP_001394662.1:p.Gln1348Ter nonsense NM_001407734.1:c.4042C>T NP_001394663.1:p.Gln1348Ter nonsense NM_001407735.1:c.4042C>T NP_001394664.1:p.Gln1348Ter nonsense NM_001407736.1:c.4042C>T NP_001394665.1:p.Gln1348Ter nonsense NM_001407737.1:c.4042C>T NP_001394666.1:p.Gln1348Ter nonsense NM_001407738.1:c.4042C>T NP_001394667.1:p.Gln1348Ter nonsense NM_001407739.1:c.4042C>T NP_001394668.1:p.Gln1348Ter nonsense NM_001407740.1:c.4039C>T NP_001394669.1:p.Gln1347Ter nonsense NM_001407741.1:c.4039C>T NP_001394670.1:p.Gln1347Ter nonsense NM_001407742.1:c.4039C>T NP_001394671.1:p.Gln1347Ter nonsense NM_001407743.1:c.4039C>T NP_001394672.1:p.Gln1347Ter nonsense NM_001407744.1:c.4039C>T NP_001394673.1:p.Gln1347Ter nonsense NM_001407745.1:c.4039C>T NP_001394674.1:p.Gln1347Ter nonsense NM_001407746.1:c.4039C>T NP_001394675.1:p.Gln1347Ter nonsense NM_001407747.1:c.4039C>T NP_001394676.1:p.Gln1347Ter nonsense NM_001407748.1:c.4039C>T NP_001394677.1:p.Gln1347Ter nonsense NM_001407749.1:c.4039C>T NP_001394678.1:p.Gln1347Ter nonsense NM_001407750.1:c.4042C>T NP_001394679.1:p.Gln1348Ter nonsense NM_001407751.1:c.4042C>T NP_001394680.1:p.Gln1348Ter nonsense NM_001407752.1:c.4042C>T NP_001394681.1:p.Gln1348Ter nonsense NM_001407838.1:c.4039C>T NP_001394767.1:p.Gln1347Ter nonsense NM_001407839.1:c.4039C>T NP_001394768.1:p.Gln1347Ter nonsense NM_001407841.1:c.4039C>T NP_001394770.1:p.Gln1347Ter nonsense NM_001407842.1:c.4039C>T NP_001394771.1:p.Gln1347Ter nonsense NM_001407843.1:c.4039C>T NP_001394772.1:p.Gln1347Ter nonsense NM_001407844.1:c.4039C>T NP_001394773.1:p.Gln1347Ter nonsense NM_001407845.1:c.4039C>T NP_001394774.1:p.Gln1347Ter nonsense NM_001407846.1:c.4039C>T NP_001394775.1:p.Gln1347Ter nonsense NM_001407847.1:c.4039C>T NP_001394776.1:p.Gln1347Ter nonsense NM_001407848.1:c.4039C>T NP_001394777.1:p.Gln1347Ter nonsense NM_001407849.1:c.4039C>T NP_001394778.1:p.Gln1347Ter nonsense NM_001407850.1:c.4042C>T NP_001394779.1:p.Gln1348Ter nonsense NM_001407851.1:c.4042C>T NP_001394780.1:p.Gln1348Ter nonsense NM_001407852.1:c.4042C>T NP_001394781.1:p.Gln1348Ter nonsense NM_001407853.1:c.3970C>T NP_001394782.1:p.Gln1324Ter nonsense NM_001407854.1:c.4183C>T NP_001394783.1:p.Gln1395Ter nonsense NM_001407858.1:c.4183C>T NP_001394787.1:p.Gln1395Ter nonsense NM_001407859.1:c.4183C>T NP_001394788.1:p.Gln1395Ter nonsense NM_001407860.1:c.4180C>T NP_001394789.1:p.Gln1394Ter nonsense NM_001407861.1:c.4180C>T NP_001394790.1:p.Gln1394Ter nonsense NM_001407862.1:c.3982C>T NP_001394791.1:p.Gln1328Ter nonsense NM_001407863.1:c.4060C>T NP_001394792.1:p.Gln1354Ter nonsense NM_001407874.1:c.3979C>T NP_001394803.1:p.Gln1327Ter nonsense NM_001407875.1:c.3979C>T NP_001394804.1:p.Gln1327Ter nonsense NM_001407879.1:c.3973C>T NP_001394808.1:p.Gln1325Ter nonsense NM_001407881.1:c.3973C>T NP_001394810.1:p.Gln1325Ter nonsense NM_001407882.1:c.3973C>T NP_001394811.1:p.Gln1325Ter nonsense NM_001407884.1:c.3973C>T NP_001394813.1:p.Gln1325Ter nonsense NM_001407885.1:c.3973C>T NP_001394814.1:p.Gln1325Ter nonsense NM_001407886.1:c.3973C>T NP_001394815.1:p.Gln1325Ter nonsense NM_001407887.1:c.3973C>T NP_001394816.1:p.Gln1325Ter nonsense NM_001407889.1:c.3973C>T NP_001394818.1:p.Gln1325Ter nonsense NM_001407894.1:c.3970C>T NP_001394823.1:p.Gln1324Ter nonsense NM_001407895.1:c.3970C>T NP_001394824.1:p.Gln1324Ter nonsense NM_001407896.1:c.3970C>T NP_001394825.1:p.Gln1324Ter nonsense NM_001407897.1:c.3970C>T NP_001394826.1:p.Gln1324Ter nonsense NM_001407898.1:c.3970C>T NP_001394827.1:p.Gln1324Ter nonsense NM_001407899.1:c.3970C>T NP_001394828.1:p.Gln1324Ter nonsense NM_001407900.1:c.3973C>T NP_001394829.1:p.Gln1325Ter nonsense NM_001407902.1:c.3973C>T NP_001394831.1:p.Gln1325Ter nonsense NM_001407904.1:c.3973C>T NP_001394833.1:p.Gln1325Ter nonsense NM_001407906.1:c.3973C>T NP_001394835.1:p.Gln1325Ter nonsense NM_001407907.1:c.3973C>T NP_001394836.1:p.Gln1325Ter nonsense NM_001407908.1:c.3973C>T NP_001394837.1:p.Gln1325Ter nonsense NM_001407909.1:c.3973C>T NP_001394838.1:p.Gln1325Ter nonsense NM_001407910.1:c.3973C>T NP_001394839.1:p.Gln1325Ter nonsense NM_001407915.1:c.3970C>T NP_001394844.1:p.Gln1324Ter nonsense NM_001407916.1:c.3970C>T NP_001394845.1:p.Gln1324Ter nonsense NM_001407917.1:c.3970C>T NP_001394846.1:p.Gln1324Ter nonsense NM_001407918.1:c.3970C>T NP_001394847.1:p.Gln1324Ter nonsense NM_001407919.1:c.4060C>T NP_001394848.1:p.Gln1354Ter nonsense NM_001407920.1:c.3919C>T NP_001394849.1:p.Gln1307Ter nonsense NM_001407921.1:c.3919C>T NP_001394850.1:p.Gln1307Ter nonsense NM_001407922.1:c.3919C>T NP_001394851.1:p.Gln1307Ter nonsense NM_001407923.1:c.3919C>T NP_001394852.1:p.Gln1307Ter nonsense NM_001407924.1:c.3919C>T NP_001394853.1:p.Gln1307Ter nonsense NM_001407925.1:c.3919C>T NP_001394854.1:p.Gln1307Ter nonsense NM_001407926.1:c.3919C>T NP_001394855.1:p.Gln1307Ter nonsense NM_001407927.1:c.3919C>T NP_001394856.1:p.Gln1307Ter nonsense NM_001407928.1:c.3919C>T NP_001394857.1:p.Gln1307Ter nonsense NM_001407929.1:c.3919C>T NP_001394858.1:p.Gln1307Ter nonsense NM_001407930.1:c.3916C>T NP_001394859.1:p.Gln1306Ter nonsense NM_001407931.1:c.3916C>T NP_001394860.1:p.Gln1306Ter nonsense NM_001407932.1:c.3916C>T NP_001394861.1:p.Gln1306Ter nonsense NM_001407933.1:c.3919C>T NP_001394862.1:p.Gln1307Ter nonsense NM_001407934.1:c.3916C>T NP_001394863.1:p.Gln1306Ter nonsense NM_001407935.1:c.3919C>T NP_001394864.1:p.Gln1307Ter nonsense NM_001407936.1:c.3916C>T NP_001394865.1:p.Gln1306Ter nonsense NM_001407937.1:c.4060C>T NP_001394866.1:p.Gln1354Ter nonsense NM_001407938.1:c.4060C>T NP_001394867.1:p.Gln1354Ter nonsense NM_001407939.1:c.4060C>T NP_001394868.1:p.Gln1354Ter nonsense NM_001407940.1:c.4057C>T NP_001394869.1:p.Gln1353Ter nonsense NM_001407941.1:c.4057C>T NP_001394870.1:p.Gln1353Ter nonsense NM_001407942.1:c.4042C>T NP_001394871.1:p.Gln1348Ter nonsense NM_001407943.1:c.4039C>T NP_001394872.1:p.Gln1347Ter nonsense NM_001407944.1:c.4042C>T NP_001394873.1:p.Gln1348Ter nonsense NM_001407945.1:c.4042C>T NP_001394874.1:p.Gln1348Ter nonsense NM_001407946.1:c.3850C>T NP_001394875.1:p.Gln1284Ter nonsense NM_001407947.1:c.3850C>T NP_001394876.1:p.Gln1284Ter nonsense NM_001407948.1:c.3850C>T NP_001394877.1:p.Gln1284Ter nonsense NM_001407949.1:c.3850C>T NP_001394878.1:p.Gln1284Ter nonsense NM_001407950.1:c.3850C>T NP_001394879.1:p.Gln1284Ter nonsense NM_001407951.1:c.3850C>T NP_001394880.1:p.Gln1284Ter nonsense NM_001407952.1:c.3850C>T NP_001394881.1:p.Gln1284Ter nonsense NM_001407953.1:c.3850C>T NP_001394882.1:p.Gln1284Ter nonsense NM_001407954.1:c.3847C>T NP_001394883.1:p.Gln1283Ter nonsense NM_001407955.1:c.3847C>T NP_001394884.1:p.Gln1283Ter nonsense NM_001407956.1:c.3847C>T NP_001394885.1:p.Gln1283Ter nonsense NM_001407957.1:c.3850C>T NP_001394886.1:p.Gln1284Ter nonsense NM_001407958.1:c.3847C>T NP_001394887.1:p.Gln1283Ter nonsense NM_001407959.1:c.3802C>T NP_001394888.1:p.Gln1268Ter nonsense NM_001407960.1:c.3802C>T NP_001394889.1:p.Gln1268Ter nonsense NM_001407962.1:c.3799C>T NP_001394891.1:p.Gln1267Ter nonsense NM_001407963.1:c.3802C>T NP_001394892.1:p.Gln1268Ter nonsense NM_001407964.1:c.4039C>T NP_001394893.1:p.Gln1347Ter nonsense NM_001407965.1:c.3679C>T NP_001394894.1:p.Gln1227Ter nonsense NM_001407966.1:c.3295C>T NP_001394895.1:p.Gln1099Ter nonsense NM_001407967.1:c.3295C>T NP_001394896.1:p.Gln1099Ter nonsense NM_001407968.1:c.1579C>T NP_001394897.1:p.Gln527Ter nonsense NM_001407969.1:c.1579C>T NP_001394898.1:p.Gln527Ter nonsense NM_001407970.1:c.874C>T NP_001394899.1:p.Gln292Ter nonsense NM_001407971.1:c.874C>T NP_001394900.1:p.Gln292Ter nonsense NM_001407972.1:c.871C>T NP_001394901.1:p.Gln291Ter nonsense NM_001407973.1:c.874C>T NP_001394902.1:p.Gln292Ter nonsense NM_001407974.1:c.874C>T NP_001394903.1:p.Gln292Ter nonsense NM_001407975.1:c.874C>T NP_001394904.1:p.Gln292Ter nonsense NM_001407976.1:c.874C>T NP_001394905.1:p.Gln292Ter nonsense NM_001407977.1:c.874C>T NP_001394906.1:p.Gln292Ter nonsense NM_001407978.1:c.874C>T NP_001394907.1:p.Gln292Ter nonsense NM_001407979.1:c.874C>T NP_001394908.1:p.Gln292Ter nonsense NM_001407980.1:c.874C>T NP_001394909.1:p.Gln292Ter nonsense NM_001407981.1:c.874C>T NP_001394910.1:p.Gln292Ter nonsense NM_001407982.1:c.874C>T NP_001394911.1:p.Gln292Ter nonsense NM_001407983.1:c.874C>T NP_001394912.1:p.Gln292Ter nonsense NM_001407984.1:c.871C>T NP_001394913.1:p.Gln291Ter nonsense NM_001407985.1:c.871C>T NP_001394914.1:p.Gln291Ter nonsense NM_001407986.1:c.871C>T NP_001394915.1:p.Gln291Ter nonsense NM_001407990.1:c.874C>T NP_001394919.1:p.Gln292Ter nonsense NM_001407991.1:c.871C>T NP_001394920.1:p.Gln291Ter nonsense NM_001407992.1:c.871C>T NP_001394921.1:p.Gln291Ter nonsense NM_001407993.1:c.874C>T NP_001394922.1:p.Gln292Ter nonsense NM_001408392.1:c.871C>T NP_001395321.1:p.Gln291Ter nonsense NM_001408396.1:c.871C>T NP_001395325.1:p.Gln291Ter nonsense NM_001408397.1:c.871C>T NP_001395326.1:p.Gln291Ter nonsense NM_001408398.1:c.871C>T NP_001395327.1:p.Gln291Ter nonsense NM_001408399.1:c.871C>T NP_001395328.1:p.Gln291Ter nonsense NM_001408400.1:c.871C>T NP_001395329.1:p.Gln291Ter nonsense NM_001408401.1:c.871C>T NP_001395330.1:p.Gln291Ter nonsense NM_001408402.1:c.871C>T NP_001395331.1:p.Gln291Ter nonsense NM_001408403.1:c.874C>T NP_001395332.1:p.Gln292Ter nonsense NM_001408404.1:c.874C>T NP_001395333.1:p.Gln292Ter nonsense NM_001408406.1:c.868C>T NP_001395335.1:p.Gln290Ter nonsense NM_001408407.1:c.871C>T NP_001395336.1:p.Gln291Ter nonsense NM_001408408.1:c.865C>T NP_001395337.1:p.Gln289Ter nonsense NM_001408409.1:c.796C>T NP_001395338.1:p.Gln266Ter nonsense NM_001408410.1:c.733C>T NP_001395339.1:p.Gln245Ter nonsense NM_001408411.1:c.796C>T NP_001395340.1:p.Gln266Ter nonsense NM_001408412.1:c.796C>T NP_001395341.1:p.Gln266Ter nonsense NM_001408413.1:c.793C>T NP_001395342.1:p.Gln265Ter nonsense NM_001408414.1:c.796C>T NP_001395343.1:p.Gln266Ter nonsense NM_001408415.1:c.796C>T NP_001395344.1:p.Gln266Ter nonsense NM_001408416.1:c.793C>T NP_001395345.1:p.Gln265Ter nonsense NM_001408418.1:c.757C>T NP_001395347.1:p.Gln253Ter nonsense NM_001408419.1:c.757C>T NP_001395348.1:p.Gln253Ter nonsense NM_001408420.1:c.757C>T NP_001395349.1:p.Gln253Ter nonsense NM_001408421.1:c.754C>T NP_001395350.1:p.Gln252Ter nonsense NM_001408422.1:c.757C>T NP_001395351.1:p.Gln253Ter nonsense NM_001408423.1:c.757C>T NP_001395352.1:p.Gln253Ter nonsense NM_001408424.1:c.754C>T NP_001395353.1:p.Gln252Ter nonsense NM_001408425.1:c.751C>T NP_001395354.1:p.Gln251Ter nonsense NM_001408426.1:c.751C>T NP_001395355.1:p.Gln251Ter nonsense NM_001408427.1:c.751C>T NP_001395356.1:p.Gln251Ter nonsense NM_001408428.1:c.751C>T NP_001395357.1:p.Gln251Ter nonsense NM_001408429.1:c.751C>T NP_001395358.1:p.Gln251Ter nonsense NM_001408430.1:c.751C>T NP_001395359.1:p.Gln251Ter nonsense NM_001408431.1:c.754C>T NP_001395360.1:p.Gln252Ter nonsense NM_001408432.1:c.748C>T NP_001395361.1:p.Gln250Ter nonsense NM_001408433.1:c.748C>T NP_001395362.1:p.Gln250Ter nonsense NM_001408434.1:c.748C>T NP_001395363.1:p.Gln250Ter nonsense NM_001408435.1:c.748C>T NP_001395364.1:p.Gln250Ter nonsense NM_001408436.1:c.751C>T NP_001395365.1:p.Gln251Ter nonsense NM_001408437.1:c.751C>T NP_001395366.1:p.Gln251Ter nonsense NM_001408438.1:c.751C>T NP_001395367.1:p.Gln251Ter nonsense NM_001408439.1:c.751C>T NP_001395368.1:p.Gln251Ter nonsense NM_001408440.1:c.751C>T NP_001395369.1:p.Gln251Ter nonsense NM_001408441.1:c.751C>T NP_001395370.1:p.Gln251Ter nonsense NM_001408442.1:c.751C>T NP_001395371.1:p.Gln251Ter nonsense NM_001408443.1:c.751C>T NP_001395372.1:p.Gln251Ter nonsense NM_001408444.1:c.751C>T NP_001395373.1:p.Gln251Ter nonsense NM_001408445.1:c.748C>T NP_001395374.1:p.Gln250Ter nonsense NM_001408446.1:c.748C>T NP_001395375.1:p.Gln250Ter nonsense NM_001408447.1:c.748C>T NP_001395376.1:p.Gln250Ter nonsense NM_001408448.1:c.748C>T NP_001395377.1:p.Gln250Ter nonsense NM_001408450.1:c.748C>T NP_001395379.1:p.Gln250Ter nonsense NM_001408451.1:c.739C>T NP_001395380.1:p.Gln247Ter nonsense NM_001408452.1:c.733C>T NP_001395381.1:p.Gln245Ter nonsense NM_001408453.1:c.733C>T NP_001395382.1:p.Gln245Ter nonsense NM_001408454.1:c.733C>T NP_001395383.1:p.Gln245Ter nonsense NM_001408455.1:c.733C>T NP_001395384.1:p.Gln245Ter nonsense NM_001408456.1:c.733C>T NP_001395385.1:p.Gln245Ter nonsense NM_001408457.1:c.733C>T NP_001395386.1:p.Gln245Ter nonsense NM_001408458.1:c.733C>T NP_001395387.1:p.Gln245Ter nonsense NM_001408459.1:c.733C>T NP_001395388.1:p.Gln245Ter nonsense NM_001408460.1:c.733C>T NP_001395389.1:p.Gln245Ter nonsense NM_001408461.1:c.733C>T NP_001395390.1:p.Gln245Ter nonsense NM_001408462.1:c.730C>T NP_001395391.1:p.Gln244Ter nonsense NM_001408463.1:c.730C>T NP_001395392.1:p.Gln244Ter nonsense NM_001408464.1:c.730C>T NP_001395393.1:p.Gln244Ter nonsense NM_001408465.1:c.730C>T NP_001395394.1:p.Gln244Ter nonsense NM_001408466.1:c.733C>T NP_001395395.1:p.Gln245Ter nonsense NM_001408467.1:c.733C>T NP_001395396.1:p.Gln245Ter nonsense NM_001408468.1:c.730C>T NP_001395397.1:p.Gln244Ter nonsense NM_001408469.1:c.733C>T NP_001395398.1:p.Gln245Ter nonsense NM_001408470.1:c.730C>T NP_001395399.1:p.Gln244Ter nonsense NM_001408472.1:c.874C>T NP_001395401.1:p.Gln292Ter nonsense NM_001408473.1:c.871C>T NP_001395402.1:p.Gln291Ter nonsense NM_001408474.1:c.673C>T NP_001395403.1:p.Gln225Ter nonsense NM_001408475.1:c.670C>T NP_001395404.1:p.Gln224Ter nonsense NM_001408476.1:c.673C>T NP_001395405.1:p.Gln225Ter nonsense NM_001408478.1:c.664C>T NP_001395407.1:p.Gln222Ter nonsense NM_001408479.1:c.664C>T NP_001395408.1:p.Gln222Ter nonsense NM_001408480.1:c.664C>T NP_001395409.1:p.Gln222Ter nonsense NM_001408481.1:c.664C>T NP_001395410.1:p.Gln222Ter nonsense NM_001408482.1:c.664C>T NP_001395411.1:p.Gln222Ter nonsense NM_001408483.1:c.664C>T NP_001395412.1:p.Gln222Ter nonsense NM_001408484.1:c.664C>T NP_001395413.1:p.Gln222Ter nonsense NM_001408485.1:c.664C>T NP_001395414.1:p.Gln222Ter nonsense NM_001408489.1:c.664C>T NP_001395418.1:p.Gln222Ter nonsense NM_001408490.1:c.661C>T NP_001395419.1:p.Gln221Ter nonsense NM_001408491.1:c.661C>T NP_001395420.1:p.Gln221Ter nonsense NM_001408492.1:c.664C>T NP_001395421.1:p.Gln222Ter nonsense NM_001408493.1:c.661C>T NP_001395422.1:p.Gln221Ter nonsense NM_001408494.1:c.634C>T NP_001395423.1:p.Gln212Ter nonsense NM_001408495.1:c.631C>T NP_001395424.1:p.Gln211Ter nonsense NM_001408496.1:c.610C>T NP_001395425.1:p.Gln204Ter nonsense NM_001408497.1:c.610C>T NP_001395426.1:p.Gln204Ter nonsense NM_001408498.1:c.610C>T NP_001395427.1:p.Gln204Ter nonsense NM_001408499.1:c.610C>T NP_001395428.1:p.Gln204Ter nonsense NM_001408500.1:c.610C>T NP_001395429.1:p.Gln204Ter nonsense NM_001408501.1:c.610C>T NP_001395430.1:p.Gln204Ter nonsense NM_001408502.1:c.541C>T NP_001395431.1:p.Gln181Ter nonsense NM_001408503.1:c.607C>T NP_001395432.1:p.Gln203Ter nonsense NM_001408504.1:c.607C>T NP_001395433.1:p.Gln203Ter nonsense NM_001408505.1:c.607C>T NP_001395434.1:p.Gln203Ter nonsense NM_001408506.1:c.547C>T NP_001395435.1:p.Gln183Ter nonsense NM_001408507.1:c.547C>T NP_001395436.1:p.Gln183Ter nonsense NM_001408508.1:c.538C>T NP_001395437.1:p.Gln180Ter nonsense NM_001408509.1:c.538C>T NP_001395438.1:p.Gln180Ter nonsense NM_001408510.1:c.493C>T NP_001395439.1:p.Gln165Ter nonsense NM_001408511.1:c.490C>T NP_001395440.1:p.Gln164Ter nonsense NM_001408512.1:c.370C>T NP_001395441.1:p.Gln124Ter nonsense NM_001408513.1:c.664C>T NP_001395442.1:p.Gln222Ter nonsense NM_001408514.1:c.664C>T NP_001395443.1:p.Gln222Ter nonsense NM_007297.4:c.4042C>T NP_009228.2:p.Gln1348Ter nonsense NM_007298.4:c.874C>T NP_009229.2:p.Gln292Ter nonsense NM_007299.4:c.874C>T NP_009230.2:p.Gln292Ter nonsense NM_007300.4:c.4183C>T NP_009231.2:p.Gln1395Ter nonsense NM_007304.2:c.874C>T NP_009235.2:p.Gln292Ter nonsense NR_027676.2:n.4360C>T non-coding transcript variant NC_000017.11:g.43090946G>A NC_000017.10:g.41242963G>A NG_005905.2:g.127038C>T LRG_292:g.127038C>T LRG_292t1:c.4183C>T LRG_292p1:p.Gln1395Ter U14680.1:n.4302C>T - Protein change
- Q1395*, Q292*, Q1348*, Q1099*, Q1284*, Q1328*, Q165*, Q181*, Q204*, Q211*, Q244*, Q245*, Q250*, Q266*, Q289*, Q1283*, Q1324*, Q1327*, Q1368*, Q164*, Q183*, Q221*, Q225*, Q247*, Q252*, Q253*, Q290*, Q1227*, Q1268*, Q1306*, Q1325*, Q1353*, Q1354*, Q1369*, Q1392*, Q203*, Q527*, Q124*, Q1267*, Q1307*, Q1347*, Q1394*, Q180*, Q212*, Q222*, Q224*, Q251*, Q265*, Q291*
- Other names
-
p.Q1395*:CAG>TAG
p.Gln1395Ter
4302C>T
- Canonical SPDI
- NC_000017.11:43090945:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
protein truncation; Variation Ontology [ VariO:0015]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13050 | 14856 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (12) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000077564.29 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2022 | RCV000162874.18 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2023 | RCV000212181.40 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2024 | RCV000496276.20 | |
| Pathogenic (1) |
no assertion criteria provided
|
Aug 9, 2013 | RCV000735467.9 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Jan 30, 2019 | RCV000778172.11 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV001353792.9 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282324.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Jan 30, 2019)
|
criteria provided, single submitter
Method: research
|
Hereditary Breast Carcinoma
Affected status: yes
Allele origin:
germline
|
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center
Accession: SCV000914330.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Number of individuals with the variant: 1
Geographic origin: Brazil
|
|
|
Pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140532.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
|
Pathogenic
(Mar 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699114.2
First in ClinVar: Aug 27, 2017 Last updated: Mar 22, 2021 |
Comment:
Variant summary: BRCA1 c.4183C>T (p.Gln1395X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.4183C>T (p.Gln1395X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 245892 control chromosomes. c.4183C>T has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Multiple clinical diagnostic laboratories, one expert panel (ENIGMA) and a consortium (CIMBA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Feb 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683156.3
First in ClinVar: Feb 19, 2018 Last updated: Jun 19, 2021 |
Comment:
This variant changes 1 nucleotide in exon 11 of the BRCA1 gene, creating a premature translation stop signal in the BRCA1 protein. This variant is … (more)
This variant changes 1 nucleotide in exon 11 of the BRCA1 gene, creating a premature translation stop signal in the BRCA1 protein. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with breast and ovarian cancer (PMID: 8531967, 16760289, 16847550, 22711857, 24728189, 26014432, 26681312, 27553291, 29470806, 30322717, 31090900) and is reported to be a founder mutation in the Tyrolean population in Austria (PMID: 26014432). This variant has been identified in 1/242836 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Nov 10, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210169.12
First in ClinVar: Feb 24, 2015 Last updated: Jul 18, 2021 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4302C>T; This variant is associated with the following publications: (PMID: 31528241, 31090900, 30322717, 29161300, 29446198, 29907814, 30720243, 29470806, 28135048, 26911350, 26681312, 27553291, 27425403, 26986251, 16287141, 25722380, 20104584, 16683254, 24728189, 19941162, 21559243, 25452441, 17949280, 14672397, 27225819, 24504028, 23772696, 16998791, 16847550, 26014432, 8531967, 22006311) (less)
|
|
|
Pathogenic
(Feb 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002580592.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4_MOD, PM2_SUP
|
Number of individuals with the variant: 2
Sex: female
|
|
|
Pathogenic
(Sep 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002600896.1
First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 |
Comment:
A heterozygous nonsense splice site proximal variation in exon 11 of the BRCA1 gene that results in a stop codon and premature truncation of the … (more)
A heterozygous nonsense splice site proximal variation in exon 11 of the BRCA1 gene that results in a stop codon and premature truncation of the protein at codon 1395 was detected . The variant is documented as pathogenic in hereditary breast ovarian cancer syndrome in the ClinVar database. The variant has not been reported in the 1000 genomes and gnomAD databases . The in-silico prediction of the variant is damaging by Mutation Taster2 tool. The reference codon is conserved across species. (less)
Clinical Features:
Breast carcinoma (present)
Age: 30-39 years
Sex: female
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000325875.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
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Likely pathogenic
(Apr 21, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220260.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
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Pathogenic
(Jun 24, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211749.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001581780.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357260, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer, ovarian cancer and peritoneal carcinoma (PMID: 8531967, 22006311, 24504028, 26681312, 27553291). This variant is also known as 4302C>T. ClinVar contains an entry for this variant (Variation ID: 55125). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213361.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.Q1395* pathogenic mutation (also known as c.4183C>T), located in coding exon 10 of the BRCA1 gene, results from a C to T substitution at … (more)
The p.Q1395* pathogenic mutation (also known as c.4183C>T), located in coding exon 10 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4183. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This mutation has been extensively reported in the literature in individuals with a personal and/or family history of breast and/or ovarian and/or peritoneal cancer and/or colon cancer and associated with somatic loss of heterozygosity (Langston AA et al. N Engl J Med. 1996 Jan 18;334(3):137-42; Walsh T et al. Proc Natl Acad Sci. U S A. 2011 Nov 1;108(44):18032-7; Cunningham JM et al. Sci Rep. 2014 Feb;4:4026; Rashid MU et al. BMC Cancer. 2016 08;16:673; Alemar B et al. Cancer Genet. 2016 09;209(9):417-422; Alemar B et al. PLoS ONE. 2017 Nov;12(11):e0187630; Palermo E et al. Sci Rep. 2018 Jun;8(1):9188; Singh J et al. Breast Cancer Res. Treat. 2018 Jul;170(1):189-196; Soyano AE et al. Clin Colorectal Cancer. 2018 12;17(4):e647-e650), as well as in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR Hum. Mutat. 2018 05;39(5):593-620). This alteration has also been shown to be highly prevalent in the Tyrolean population of Austria (Pölsler L et al. Eur. J. Hum. Genet. 2016 Feb;24:258-62). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447558.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Breast carcinoma (present)
Sex: female
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004048576.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant has been reported in individuals and families affected with breast cancer, ovarian cancer and peritoneal carcinoma (Walsh T et al). The variant is … (more)
This variant has been reported in individuals and families affected with breast cancer, ovarian cancer and peritoneal carcinoma (Walsh T et al). The variant is reported with the allele frequency of 0.0004118% in gnomAD database and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (Borg A et al.). The nucleotide change in BRCA1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Breast carcinoma (present)
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Pathogenic
(Jul 22, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296397.5
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in numerous individuals/families with hereditary breast/ovarian cancer syndrome in the published … (more)
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in numerous individuals/families with hereditary breast/ovarian cancer syndrome in the published literature (PMID: 31528241 (2019), 31090900 (2019), 30322717 (2018), 29907814 (2018), 29470806 (2018), 29446198 (2018), 29161300 (2017), 27553291 (2016), 27425403 (2016), 26681312 (2015), 26014432 (2015), 24728189 (2014), 24504028 (2014), 23772696 (2014), 22006311 (2011), 16998791 (2006), 16847550 (2006), 11802209 (2002), 8531967 (1996)). (less)
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Pathogenic
(Jul 29, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003818082.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Feb 01, 2023)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247350.23
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
BRCA1: PVS1, PM2, PP1, PS4:Supporting
Number of individuals with the variant: 1
|
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145005.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 548
Observation 2:
Number of individuals with the variant: 2
Geographic origin: Germany
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 4:
Number of individuals with the variant: 4
Ethnicity/Population group: Austrian
Geographic origin: Austria
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: France
Observation 6:
Number of individuals with the variant: 6
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 7:
Number of individuals with the variant: 8
Ethnicity/Population group: Western European
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Pathogenic
(Sep 17, 2012)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000109366.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
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|
Pathogenic
(Feb 11, 2015)
|
no assertion criteria provided
(clinical testing)
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Medical University Innsbruck
Study: BRCA-Tyrol
Accession: SCV000212002.1 First in ClinVar: Mar 03, 2015 Last updated: Mar 03, 2015
Comment:
BRCA-mutation spectrum Western Austria
|
Number of individuals with the variant: 14
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906261.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587380.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733613.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Aug 09, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863604.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
|
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591497.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Gln1395X variant has been previously reported in the literature in 2 of 512 proband chromosomes from individuals with hereditary breast and ovarian cancer and … (more)
The p.Gln1395X variant has been previously reported in the literature in 2 of 512 proband chromosomes from individuals with hereditary breast and ovarian cancer and absent from 100 control chromosomes (Langston 1996, Rashid 2006). In addition, this variant is reported in the BIC database 28x as clinically important and the UMD database 35x as causal. This variant leads to a premature stop codon at position 1395, which is predicted to lead to a truncated or absent protein product and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic. (less)
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Sep 25, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Diagnostics Centre, Carl Von Ossietzky University Oldenburg
Accession: SCV004174184.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
Comment:
The variant BRCA1:c.4183C>T p.(Gln1395Ter) , which is located in the coding exon 11 of the BRCA1 gene, results from a cytosine-to-thymine substitution at nucleotide position … (more)
The variant BRCA1:c.4183C>T p.(Gln1395Ter) , which is located in the coding exon 11 of the BRCA1 gene, results from a cytosine-to-thymine substitution at nucleotide position 4183. The glutamine at protein position 1395 is replaced by a premature stop codon which is predicted to cause protein truncation or absence due to non-sense mediated decay. The variant has already been extensively published in unrelated individuals with personal and fammilial history of breast cancer (PMID: 29446198, 22006311, 8531967, 30322717) and also co-segregates with the disease (PMID: 15340362, 20104584, 29907814). It is considered a Tyrolean founder mutation (PMID: 26014432). In the ClinVar database, the variant have multiple entries (25) for Pathogenic or Likely pathogenic (VCV000055125.41) and is assessed as Pathogenic by the ENIGMA expert committee. This variant is very rare in the overall population (no carriers in gnomAD, gnomAD V3.1.2). The variant is classified as Pathogenic. (less)
Number of individuals with the variant: 1
Age: 50-59 years
Sex: female
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Comment:
Comment:
Variant summary: BRCA1 c.4183C>T (p.Gln1395X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 245892 control chromosomes. c.4183C>T has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Multiple clinical diagnostic laboratories, one expert panel (ENIGMA) and a consortium (CIMBA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 11 of the BRCA1 gene, creating a premature translation stop signal in the BRCA1 protein. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with breast and ovarian cancer (PMID: 8531967, 16760289, 16847550, 22711857, 24728189, 26014432, 26681312, 27553291, 29470806, 30322717, 31090900) and is reported to be a founder mutation in the Tyrolean population in Austria (PMID: 26014432). This variant has been identified in 1/242836 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4302C>T; This variant is associated with the following publications: (PMID: 31528241, 31090900, 30322717, 29161300, 29446198, 29907814, 30720243, 29470806, 28135048, 26911350, 26681312, 27553291, 27425403, 26986251, 16287141, 25722380, 20104584, 16683254, 24728189, 19941162, 21559243, 25452441, 17949280, 14672397, 27225819, 24504028, 23772696, 16998791, 16847550, 26014432, 8531967, 22006311)
Comment:
A heterozygous nonsense splice site proximal variation in exon 11 of the BRCA1 gene that results in a stop codon and premature truncation of the protein at codon 1395 was detected . The variant is documented as pathogenic in hereditary breast ovarian cancer syndrome in the ClinVar database. The variant has not been reported in the 1000 genomes and gnomAD databases . The in-silico prediction of the variant is damaging by Mutation Taster2 tool. The reference codon is conserved across species.
Comment:
This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357260, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer, ovarian cancer and peritoneal carcinoma (PMID: 8531967, 22006311, 24504028, 26681312, 27553291). This variant is also known as 4302C>T. ClinVar contains an entry for this variant (Variation ID: 55125). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Q1395* pathogenic mutation (also known as c.4183C>T), located in coding exon 10 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4183. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This mutation has been extensively reported in the literature in individuals with a personal and/or family history of breast and/or ovarian and/or peritoneal cancer and/or colon cancer and associated with somatic loss of heterozygosity (Langston AA et al. N Engl J Med. 1996 Jan 18;334(3):137-42; Walsh T et al. Proc Natl Acad Sci. U S A. 2011 Nov 1;108(44):18032-7; Cunningham JM et al. Sci Rep. 2014 Feb;4:4026; Rashid MU et al. BMC Cancer. 2016 08;16:673; Alemar B et al. Cancer Genet. 2016 09;209(9):417-422; Alemar B et al. PLoS ONE. 2017 Nov;12(11):e0187630; Palermo E et al. Sci Rep. 2018 Jun;8(1):9188; Singh J et al. Breast Cancer Res. Treat. 2018 Jul;170(1):189-196; Soyano AE et al. Clin Colorectal Cancer. 2018 12;17(4):e647-e650), as well as in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR Hum. Mutat. 2018 05;39(5):593-620). This alteration has also been shown to be highly prevalent in the Tyrolean population of Austria (Pölsler L et al. Eur. J. Hum. Genet. 2016 Feb;24:258-62). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
This variant has been reported in individuals and families affected with breast cancer, ovarian cancer and peritoneal carcinoma (Walsh T et al). The variant is reported with the allele frequency of 0.0004118% in gnomAD database and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (Borg A et al.). The nucleotide change in BRCA1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in numerous individuals/families with hereditary breast/ovarian cancer syndrome in the published literature (PMID: 31528241 (2019), 31090900 (2019), 30322717 (2018), 29907814 (2018), 29470806 (2018), 29446198 (2018), 29161300 (2017), 27553291 (2016), 27425403 (2016), 26681312 (2015), 26014432 (2015), 24728189 (2014), 24504028 (2014), 23772696 (2014), 22006311 (2011), 16998791 (2006), 16847550 (2006), 11802209 (2002), 8531967 (1996)).
Comment:
BRCA1: PVS1, PM2, PP1, PS4:Supporting
Comment:
The p.Gln1395X variant has been previously reported in the literature in 2 of 512 proband chromosomes from individuals with hereditary breast and ovarian cancer and absent from 100 control chromosomes (Langston 1996, Rashid 2006). In addition, this variant is reported in the BIC database 28x as clinically important and the UMD database 35x as causal. This variant leads to a premature stop codon at position 1395, which is predicted to lead to a truncated or absent protein product and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic.
Comment:
The variant BRCA1:c.4183C>T p.(Gln1395Ter) , which is located in the coding exon 11 of the BRCA1 gene, results from a cytosine-to-thymine substitution at nucleotide position 4183. The glutamine at protein position 1395 is replaced by a premature stop codon which is predicted to cause protein truncation or absence due to non-sense mediated decay. The variant has already been extensively published in unrelated individuals with personal and fammilial history of breast cancer (PMID: 29446198, 22006311, 8531967, 30322717) and also co-segregates with the disease (PMID: 15340362, 20104584, 29907814). It is considered a Tyrolean founder mutation (PMID: 26014432). In the ClinVar database, the variant have multiple entries (25) for Pathogenic or Likely pathogenic (VCV000055125.41) and is assessed as Pathogenic by the ENIGMA expert committee. This variant is very rare in the overall population (no carriers in gnomAD, gnomAD V3.1.2). The variant is classified as Pathogenic.
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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protein truncation
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002600896.1
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|
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
Variant summary: BRCA1 c.4183C>T (p.Gln1395X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 245892 control chromosomes. c.4183C>T has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Multiple clinical diagnostic laboratories, one expert panel (ENIGMA) and a consortium (CIMBA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 11 of the BRCA1 gene, creating a premature translation stop signal in the BRCA1 protein. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with breast and ovarian cancer (PMID: 8531967, 16760289, 16847550, 22711857, 24728189, 26014432, 26681312, 27553291, 29470806, 30322717, 31090900) and is reported to be a founder mutation in the Tyrolean population in Austria (PMID: 26014432). This variant has been identified in 1/242836 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4302C>T; This variant is associated with the following publications: (PMID: 31528241, 31090900, 30322717, 29161300, 29446198, 29907814, 30720243, 29470806, 28135048, 26911350, 26681312, 27553291, 27425403, 26986251, 16287141, 25722380, 20104584, 16683254, 24728189, 19941162, 21559243, 25452441, 17949280, 14672397, 27225819, 24504028, 23772696, 16998791, 16847550, 26014432, 8531967, 22006311)
Comment:
A heterozygous nonsense splice site proximal variation in exon 11 of the BRCA1 gene that results in a stop codon and premature truncation of the protein at codon 1395 was detected . The variant is documented as pathogenic in hereditary breast ovarian cancer syndrome in the ClinVar database. The variant has not been reported in the 1000 genomes and gnomAD databases . The in-silico prediction of the variant is damaging by Mutation Taster2 tool. The reference codon is conserved across species.
Comment:
This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357260, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer, ovarian cancer and peritoneal carcinoma (PMID: 8531967, 22006311, 24504028, 26681312, 27553291). This variant is also known as 4302C>T. ClinVar contains an entry for this variant (Variation ID: 55125). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Q1395* pathogenic mutation (also known as c.4183C>T), located in coding exon 10 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4183. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This mutation has been extensively reported in the literature in individuals with a personal and/or family history of breast and/or ovarian and/or peritoneal cancer and/or colon cancer and associated with somatic loss of heterozygosity (Langston AA et al. N Engl J Med. 1996 Jan 18;334(3):137-42; Walsh T et al. Proc Natl Acad Sci. U S A. 2011 Nov 1;108(44):18032-7; Cunningham JM et al. Sci Rep. 2014 Feb;4:4026; Rashid MU et al. BMC Cancer. 2016 08;16:673; Alemar B et al. Cancer Genet. 2016 09;209(9):417-422; Alemar B et al. PLoS ONE. 2017 Nov;12(11):e0187630; Palermo E et al. Sci Rep. 2018 Jun;8(1):9188; Singh J et al. Breast Cancer Res. Treat. 2018 Jul;170(1):189-196; Soyano AE et al. Clin Colorectal Cancer. 2018 12;17(4):e647-e650), as well as in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR Hum. Mutat. 2018 05;39(5):593-620). This alteration has also been shown to be highly prevalent in the Tyrolean population of Austria (Pölsler L et al. Eur. J. Hum. Genet. 2016 Feb;24:258-62). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
This variant has been reported in individuals and families affected with breast cancer, ovarian cancer and peritoneal carcinoma (Walsh T et al). The variant is reported with the allele frequency of 0.0004118% in gnomAD database and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1395*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (Borg A et al.). The nucleotide change in BRCA1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in numerous individuals/families with hereditary breast/ovarian cancer syndrome in the published literature (PMID: 31528241 (2019), 31090900 (2019), 30322717 (2018), 29907814 (2018), 29470806 (2018), 29446198 (2018), 29161300 (2017), 27553291 (2016), 27425403 (2016), 26681312 (2015), 26014432 (2015), 24728189 (2014), 24504028 (2014), 23772696 (2014), 22006311 (2011), 16998791 (2006), 16847550 (2006), 11802209 (2002), 8531967 (1996)).
Comment:
BRCA1: PVS1, PM2, PP1, PS4:Supporting
Comment:
The p.Gln1395X variant has been previously reported in the literature in 2 of 512 proband chromosomes from individuals with hereditary breast and ovarian cancer and absent from 100 control chromosomes (Langston 1996, Rashid 2006). In addition, this variant is reported in the BIC database 28x as clinically important and the UMD database 35x as causal. This variant leads to a premature stop codon at position 1395, which is predicted to lead to a truncated or absent protein product and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic.
Comment:
The variant BRCA1:c.4183C>T p.(Gln1395Ter) , which is located in the coding exon 11 of the BRCA1 gene, results from a cytosine-to-thymine substitution at nucleotide position 4183. The glutamine at protein position 1395 is replaced by a premature stop codon which is predicted to cause protein truncation or absence due to non-sense mediated decay. The variant has already been extensively published in unrelated individuals with personal and fammilial history of breast cancer (PMID: 29446198, 22006311, 8531967, 30322717) and also co-segregates with the disease (PMID: 15340362, 20104584, 29907814). It is considered a Tyrolean founder mutation (PMID: 26014432). In the ClinVar database, the variant have multiple entries (25) for Pathogenic or Likely pathogenic (VCV000055125.41) and is assessed as Pathogenic by the ENIGMA expert committee. This variant is very rare in the overall population (no carriers in gnomAD, gnomAD V3.1.2). The variant is classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study. | Rashid MU | Hereditary cancer in clinical practice | 2019 | PMID: 31528241 |
| Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers. | Nones K | Annals of oncology : official journal of the European Society for Medical Oncology | 2019 | PMID: 31090900 |
| Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. | Singh J | Breast cancer research and treatment | 2018 | PMID: 29470806 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil: Are international testing criteria appropriate for this specific population? | Alemar B | PloS one | 2017 | PMID: 29161300 |
| High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients. | Rashid MU | BMC cancer | 2016 | PMID: 27553291 |
| Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. | Alemar B | Cancer genetics | 2016 | PMID: 27425403 |
| Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
| High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing. | Pölsler L | European journal of human genetics : EJHG | 2016 | PMID: 26014432 |
| The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
| Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
| Clinical implications of genetic testing for BRCA1 and BRCA2 mutations in Austria. | Singer CF | Clinical genetics | 2014 | PMID: 23772696 |
| Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. | Walsh T | Proceedings of the National Academy of Sciences of the United States of America | 2011 | PMID: 22006311 |
| Breast and Ovarian Cancer Risk due to Prevalence of BRCA1 and BRCA2 Variants in Pakistani Population: A Pakistani Database Report. | Farooq A | Journal of oncology | 2011 | PMID: 21559243 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. | Rashid MU | International journal of cancer | 2006 | PMID: 16998791 |
| Novel BRCA1 and BRCA2 germline mutations and assessment of mutation spectrum and prevalence in Italian breast and/or ovarian cancer families. | Giannini G | Breast cancer research and treatment | 2006 | PMID: 16847550 |
| Evolutionary conservation analysis increases the colocalization of predicted exonic splicing enhancers in the BRCA1 gene with missense sequence changes and in-frame deletions, but not polymorphisms. | Pettigrew C | Breast cancer research : BCR | 2005 | PMID: 16280041 |
| Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. | Marroni F | European journal of human genetics : EJHG | 2004 | PMID: 15340362 |
| Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. | Meindl A | International journal of cancer | 2002 | PMID: 11802209 |
| BRCA1 mutations in a population-based sample of young women with breast cancer. | Langston AA | The New England journal of medicine | 1996 | PMID: 8531967 |
| Renal dysfunction after angiography; a risk factor analysis in patients with peripheral vascular disease. | Gussenhoven MJ | The Journal of cardiovascular surgery | 1991 | PMID: 2010458 |
| Wagner et al. Int. J. Cancer, in press | - | - | - | - |
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Text-mined citations for rs80357260 ...
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Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.