Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.241C>T (p.Gln81Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 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.241C>T (p.Gln81Ter)
Variation ID: 54565 Accession: VCV000054565.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43104928 (GRCh38) [ NCBI UCSC ] 17: 41256945 (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 May 1, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.241C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln81Ter nonsense NM_001407571.1:c.31C>T NP_001394500.1:p.Gln11Ter nonsense NM_001407581.1:c.241C>T NP_001394510.1:p.Gln81Ter nonsense NM_001407582.1:c.241C>T NP_001394511.1:p.Gln81Ter nonsense NM_001407583.1:c.241C>T NP_001394512.1:p.Gln81Ter nonsense NM_001407585.1:c.241C>T NP_001394514.1:p.Gln81Ter nonsense NM_001407587.1:c.241C>T NP_001394516.1:p.Gln81Ter nonsense NM_001407590.1:c.241C>T NP_001394519.1:p.Gln81Ter nonsense NM_001407591.1:c.241C>T NP_001394520.1:p.Gln81Ter nonsense NM_001407593.1:c.241C>T NP_001394522.1:p.Gln81Ter nonsense NM_001407594.1:c.241C>T NP_001394523.1:p.Gln81Ter nonsense NM_001407596.1:c.241C>T NP_001394525.1:p.Gln81Ter nonsense NM_001407597.1:c.241C>T NP_001394526.1:p.Gln81Ter nonsense NM_001407598.1:c.241C>T NP_001394527.1:p.Gln81Ter nonsense NM_001407602.1:c.241C>T NP_001394531.1:p.Gln81Ter nonsense NM_001407603.1:c.241C>T NP_001394532.1:p.Gln81Ter nonsense NM_001407605.1:c.241C>T NP_001394534.1:p.Gln81Ter nonsense NM_001407610.1:c.241C>T NP_001394539.1:p.Gln81Ter nonsense NM_001407611.1:c.241C>T NP_001394540.1:p.Gln81Ter nonsense NM_001407612.1:c.241C>T NP_001394541.1:p.Gln81Ter nonsense NM_001407613.1:c.241C>T NP_001394542.1:p.Gln81Ter nonsense NM_001407614.1:c.241C>T NP_001394543.1:p.Gln81Ter nonsense NM_001407615.1:c.241C>T NP_001394544.1:p.Gln81Ter nonsense NM_001407616.1:c.241C>T NP_001394545.1:p.Gln81Ter nonsense NM_001407617.1:c.241C>T NP_001394546.1:p.Gln81Ter nonsense NM_001407618.1:c.241C>T NP_001394547.1:p.Gln81Ter nonsense NM_001407619.1:c.241C>T NP_001394548.1:p.Gln81Ter nonsense NM_001407620.1:c.241C>T NP_001394549.1:p.Gln81Ter nonsense NM_001407621.1:c.241C>T NP_001394550.1:p.Gln81Ter nonsense NM_001407622.1:c.241C>T NP_001394551.1:p.Gln81Ter nonsense NM_001407623.1:c.241C>T NP_001394552.1:p.Gln81Ter nonsense NM_001407624.1:c.241C>T NP_001394553.1:p.Gln81Ter nonsense NM_001407625.1:c.241C>T NP_001394554.1:p.Gln81Ter nonsense NM_001407626.1:c.241C>T NP_001394555.1:p.Gln81Ter nonsense NM_001407627.1:c.241C>T NP_001394556.1:p.Gln81Ter nonsense NM_001407628.1:c.241C>T NP_001394557.1:p.Gln81Ter nonsense NM_001407629.1:c.241C>T NP_001394558.1:p.Gln81Ter nonsense NM_001407630.1:c.241C>T NP_001394559.1:p.Gln81Ter nonsense NM_001407631.1:c.241C>T NP_001394560.1:p.Gln81Ter nonsense NM_001407632.1:c.241C>T NP_001394561.1:p.Gln81Ter nonsense NM_001407633.1:c.241C>T NP_001394562.1:p.Gln81Ter nonsense NM_001407634.1:c.241C>T NP_001394563.1:p.Gln81Ter nonsense NM_001407635.1:c.241C>T NP_001394564.1:p.Gln81Ter nonsense NM_001407636.1:c.241C>T NP_001394565.1:p.Gln81Ter nonsense NM_001407637.1:c.241C>T NP_001394566.1:p.Gln81Ter nonsense NM_001407638.1:c.241C>T NP_001394567.1:p.Gln81Ter nonsense NM_001407639.1:c.241C>T NP_001394568.1:p.Gln81Ter nonsense NM_001407640.1:c.241C>T NP_001394569.1:p.Gln81Ter nonsense NM_001407641.1:c.241C>T NP_001394570.1:p.Gln81Ter nonsense NM_001407642.1:c.241C>T NP_001394571.1:p.Gln81Ter nonsense NM_001407644.1:c.241C>T NP_001394573.1:p.Gln81Ter nonsense NM_001407645.1:c.241C>T NP_001394574.1:p.Gln81Ter nonsense NM_001407646.1:c.241C>T NP_001394575.1:p.Gln81Ter nonsense NM_001407647.1:c.241C>T NP_001394576.1:p.Gln81Ter nonsense NM_001407648.1:c.241C>T NP_001394577.1:p.Gln81Ter nonsense NM_001407649.1:c.241C>T NP_001394578.1:p.Gln81Ter nonsense NM_001407652.1:c.241C>T NP_001394581.1:p.Gln81Ter nonsense NM_001407653.1:c.163C>T NP_001394582.1:p.Gln55Ter nonsense NM_001407654.1:c.163C>T NP_001394583.1:p.Gln55Ter nonsense NM_001407655.1:c.163C>T NP_001394584.1:p.Gln55Ter nonsense NM_001407656.1:c.163C>T NP_001394585.1:p.Gln55Ter nonsense NM_001407657.1:c.163C>T NP_001394586.1:p.Gln55Ter nonsense NM_001407658.1:c.163C>T NP_001394587.1:p.Gln55Ter nonsense NM_001407659.1:c.163C>T NP_001394588.1:p.Gln55Ter nonsense NM_001407660.1:c.163C>T NP_001394589.1:p.Gln55Ter nonsense NM_001407661.1:c.163C>T NP_001394590.1:p.Gln55Ter nonsense NM_001407662.1:c.163C>T NP_001394591.1:p.Gln55Ter nonsense NM_001407663.1:c.163C>T NP_001394592.1:p.Gln55Ter nonsense NM_001407664.1:c.241C>T NP_001394593.1:p.Gln81Ter nonsense NM_001407665.1:c.241C>T NP_001394594.1:p.Gln81Ter nonsense NM_001407666.1:c.241C>T NP_001394595.1:p.Gln81Ter nonsense NM_001407667.1:c.241C>T NP_001394596.1:p.Gln81Ter nonsense NM_001407668.1:c.241C>T NP_001394597.1:p.Gln81Ter nonsense NM_001407669.1:c.241C>T NP_001394598.1:p.Gln81Ter nonsense NM_001407670.1:c.241C>T NP_001394599.1:p.Gln81Ter nonsense NM_001407671.1:c.241C>T NP_001394600.1:p.Gln81Ter nonsense NM_001407672.1:c.241C>T NP_001394601.1:p.Gln81Ter nonsense NM_001407673.1:c.241C>T NP_001394602.1:p.Gln81Ter nonsense NM_001407674.1:c.241C>T NP_001394603.1:p.Gln81Ter nonsense NM_001407675.1:c.241C>T NP_001394604.1:p.Gln81Ter nonsense NM_001407676.1:c.241C>T NP_001394605.1:p.Gln81Ter nonsense NM_001407677.1:c.241C>T NP_001394606.1:p.Gln81Ter nonsense NM_001407678.1:c.241C>T NP_001394607.1:p.Gln81Ter nonsense NM_001407679.1:c.241C>T NP_001394608.1:p.Gln81Ter nonsense NM_001407680.1:c.241C>T NP_001394609.1:p.Gln81Ter nonsense NM_001407681.1:c.241C>T NP_001394610.1:p.Gln81Ter nonsense NM_001407682.1:c.241C>T NP_001394611.1:p.Gln81Ter nonsense NM_001407683.1:c.241C>T NP_001394612.1:p.Gln81Ter nonsense NM_001407684.1:c.241C>T NP_001394613.1:p.Gln81Ter nonsense NM_001407685.1:c.241C>T NP_001394614.1:p.Gln81Ter nonsense NM_001407686.1:c.241C>T NP_001394615.1:p.Gln81Ter nonsense NM_001407687.1:c.241C>T NP_001394616.1:p.Gln81Ter nonsense NM_001407688.1:c.241C>T NP_001394617.1:p.Gln81Ter nonsense NM_001407689.1:c.241C>T NP_001394618.1:p.Gln81Ter nonsense NM_001407690.1:c.241C>T NP_001394619.1:p.Gln81Ter nonsense NM_001407691.1:c.241C>T NP_001394620.1:p.Gln81Ter nonsense NM_001407692.1:c.100C>T NP_001394621.1:p.Gln34Ter nonsense NM_001407694.1:c.100C>T NP_001394623.1:p.Gln34Ter nonsense NM_001407695.1:c.100C>T NP_001394624.1:p.Gln34Ter nonsense NM_001407696.1:c.100C>T NP_001394625.1:p.Gln34Ter nonsense NM_001407697.1:c.100C>T NP_001394626.1:p.Gln34Ter nonsense NM_001407698.1:c.100C>T NP_001394627.1:p.Gln34Ter nonsense NM_001407724.1:c.100C>T NP_001394653.1:p.Gln34Ter nonsense NM_001407725.1:c.100C>T NP_001394654.1:p.Gln34Ter nonsense NM_001407726.1:c.100C>T NP_001394655.1:p.Gln34Ter nonsense NM_001407727.1:c.100C>T NP_001394656.1:p.Gln34Ter nonsense NM_001407728.1:c.100C>T NP_001394657.1:p.Gln34Ter nonsense NM_001407729.1:c.100C>T NP_001394658.1:p.Gln34Ter nonsense NM_001407730.1:c.100C>T NP_001394659.1:p.Gln34Ter nonsense NM_001407731.1:c.100C>T NP_001394660.1:p.Gln34Ter nonsense NM_001407732.1:c.100C>T NP_001394661.1:p.Gln34Ter nonsense NM_001407733.1:c.100C>T NP_001394662.1:p.Gln34Ter nonsense NM_001407734.1:c.100C>T NP_001394663.1:p.Gln34Ter nonsense NM_001407735.1:c.100C>T NP_001394664.1:p.Gln34Ter nonsense NM_001407736.1:c.100C>T NP_001394665.1:p.Gln34Ter nonsense NM_001407737.1:c.100C>T NP_001394666.1:p.Gln34Ter nonsense NM_001407738.1:c.100C>T NP_001394667.1:p.Gln34Ter nonsense NM_001407739.1:c.100C>T NP_001394668.1:p.Gln34Ter nonsense NM_001407740.1:c.100C>T NP_001394669.1:p.Gln34Ter nonsense NM_001407741.1:c.100C>T NP_001394670.1:p.Gln34Ter nonsense NM_001407742.1:c.100C>T NP_001394671.1:p.Gln34Ter nonsense NM_001407743.1:c.100C>T NP_001394672.1:p.Gln34Ter nonsense NM_001407744.1:c.100C>T NP_001394673.1:p.Gln34Ter nonsense NM_001407745.1:c.100C>T NP_001394674.1:p.Gln34Ter nonsense NM_001407746.1:c.100C>T NP_001394675.1:p.Gln34Ter nonsense NM_001407747.1:c.100C>T NP_001394676.1:p.Gln34Ter nonsense NM_001407748.1:c.100C>T NP_001394677.1:p.Gln34Ter nonsense NM_001407749.1:c.100C>T NP_001394678.1:p.Gln34Ter nonsense NM_001407750.1:c.100C>T NP_001394679.1:p.Gln34Ter nonsense NM_001407751.1:c.100C>T NP_001394680.1:p.Gln34Ter nonsense NM_001407752.1:c.100C>T NP_001394681.1:p.Gln34Ter nonsense NM_001407838.1:c.100C>T NP_001394767.1:p.Gln34Ter nonsense NM_001407839.1:c.100C>T NP_001394768.1:p.Gln34Ter nonsense NM_001407841.1:c.100C>T NP_001394770.1:p.Gln34Ter nonsense NM_001407842.1:c.100C>T NP_001394771.1:p.Gln34Ter nonsense NM_001407843.1:c.100C>T NP_001394772.1:p.Gln34Ter nonsense NM_001407844.1:c.100C>T NP_001394773.1:p.Gln34Ter nonsense NM_001407845.1:c.100C>T NP_001394774.1:p.Gln34Ter nonsense NM_001407846.1:c.100C>T NP_001394775.1:p.Gln34Ter nonsense NM_001407847.1:c.100C>T NP_001394776.1:p.Gln34Ter nonsense NM_001407848.1:c.100C>T NP_001394777.1:p.Gln34Ter nonsense NM_001407849.1:c.100C>T NP_001394778.1:p.Gln34Ter nonsense NM_001407850.1:c.100C>T NP_001394779.1:p.Gln34Ter nonsense NM_001407851.1:c.100C>T NP_001394780.1:p.Gln34Ter nonsense NM_001407852.1:c.100C>T NP_001394781.1:p.Gln34Ter nonsense NM_001407853.1:c.31C>T NP_001394782.1:p.Gln11Ter nonsense NM_001407854.1:c.241C>T NP_001394783.1:p.Gln81Ter nonsense NM_001407858.1:c.241C>T NP_001394787.1:p.Gln81Ter nonsense NM_001407859.1:c.241C>T NP_001394788.1:p.Gln81Ter nonsense NM_001407860.1:c.241C>T NP_001394789.1:p.Gln81Ter nonsense NM_001407861.1:c.241C>T NP_001394790.1:p.Gln81Ter nonsense NM_001407862.1:c.163C>T NP_001394791.1:p.Gln55Ter nonsense NM_001407863.1:c.241C>T NP_001394792.1:p.Gln81Ter nonsense NM_001407874.1:c.163C>T NP_001394803.1:p.Gln55Ter nonsense NM_001407875.1:c.163C>T NP_001394804.1:p.Gln55Ter nonsense NM_001407879.1:c.31C>T NP_001394808.1:p.Gln11Ter nonsense NM_001407881.1:c.31C>T NP_001394810.1:p.Gln11Ter nonsense NM_001407882.1:c.31C>T NP_001394811.1:p.Gln11Ter nonsense NM_001407884.1:c.31C>T NP_001394813.1:p.Gln11Ter nonsense NM_001407885.1:c.31C>T NP_001394814.1:p.Gln11Ter nonsense NM_001407886.1:c.31C>T NP_001394815.1:p.Gln11Ter nonsense NM_001407887.1:c.31C>T NP_001394816.1:p.Gln11Ter nonsense NM_001407889.1:c.31C>T NP_001394818.1:p.Gln11Ter nonsense NM_001407894.1:c.31C>T NP_001394823.1:p.Gln11Ter nonsense NM_001407895.1:c.31C>T NP_001394824.1:p.Gln11Ter nonsense NM_001407896.1:c.31C>T NP_001394825.1:p.Gln11Ter nonsense NM_001407897.1:c.31C>T NP_001394826.1:p.Gln11Ter nonsense NM_001407898.1:c.31C>T NP_001394827.1:p.Gln11Ter nonsense NM_001407899.1:c.31C>T NP_001394828.1:p.Gln11Ter nonsense NM_001407900.1:c.31C>T NP_001394829.1:p.Gln11Ter nonsense NM_001407902.1:c.31C>T NP_001394831.1:p.Gln11Ter nonsense NM_001407904.1:c.31C>T NP_001394833.1:p.Gln11Ter nonsense NM_001407906.1:c.31C>T NP_001394835.1:p.Gln11Ter nonsense NM_001407907.1:c.31C>T NP_001394836.1:p.Gln11Ter nonsense NM_001407908.1:c.31C>T NP_001394837.1:p.Gln11Ter nonsense NM_001407909.1:c.31C>T NP_001394838.1:p.Gln11Ter nonsense NM_001407910.1:c.31C>T NP_001394839.1:p.Gln11Ter nonsense NM_001407915.1:c.31C>T NP_001394844.1:p.Gln11Ter nonsense NM_001407916.1:c.31C>T NP_001394845.1:p.Gln11Ter nonsense NM_001407917.1:c.31C>T NP_001394846.1:p.Gln11Ter nonsense NM_001407918.1:c.31C>T NP_001394847.1:p.Gln11Ter nonsense NM_001407919.1:c.241C>T NP_001394848.1:p.Gln81Ter nonsense NM_001407920.1:c.100C>T NP_001394849.1:p.Gln34Ter nonsense NM_001407921.1:c.100C>T NP_001394850.1:p.Gln34Ter nonsense NM_001407922.1:c.100C>T NP_001394851.1:p.Gln34Ter nonsense NM_001407923.1:c.100C>T NP_001394852.1:p.Gln34Ter nonsense NM_001407924.1:c.100C>T NP_001394853.1:p.Gln34Ter nonsense NM_001407925.1:c.100C>T NP_001394854.1:p.Gln34Ter nonsense NM_001407926.1:c.100C>T NP_001394855.1:p.Gln34Ter nonsense NM_001407927.1:c.100C>T NP_001394856.1:p.Gln34Ter nonsense NM_001407928.1:c.100C>T NP_001394857.1:p.Gln34Ter nonsense NM_001407929.1:c.100C>T NP_001394858.1:p.Gln34Ter nonsense NM_001407930.1:c.100C>T NP_001394859.1:p.Gln34Ter nonsense NM_001407931.1:c.100C>T NP_001394860.1:p.Gln34Ter nonsense NM_001407932.1:c.100C>T NP_001394861.1:p.Gln34Ter nonsense NM_001407933.1:c.100C>T NP_001394862.1:p.Gln34Ter nonsense NM_001407934.1:c.100C>T NP_001394863.1:p.Gln34Ter nonsense NM_001407935.1:c.100C>T NP_001394864.1:p.Gln34Ter nonsense NM_001407936.1:c.100C>T NP_001394865.1:p.Gln34Ter nonsense NM_001407937.1:c.241C>T NP_001394866.1:p.Gln81Ter nonsense NM_001407938.1:c.241C>T NP_001394867.1:p.Gln81Ter nonsense NM_001407939.1:c.241C>T NP_001394868.1:p.Gln81Ter nonsense NM_001407940.1:c.241C>T NP_001394869.1:p.Gln81Ter nonsense NM_001407941.1:c.241C>T NP_001394870.1:p.Gln81Ter nonsense NM_001407942.1:c.100C>T NP_001394871.1:p.Gln34Ter nonsense NM_001407943.1:c.100C>T NP_001394872.1:p.Gln34Ter nonsense NM_001407944.1:c.100C>T NP_001394873.1:p.Gln34Ter nonsense NM_001407945.1:c.100C>T NP_001394874.1:p.Gln34Ter nonsense NM_001407946.1:c.31C>T NP_001394875.1:p.Gln11Ter nonsense NM_001407947.1:c.31C>T NP_001394876.1:p.Gln11Ter nonsense NM_001407948.1:c.31C>T NP_001394877.1:p.Gln11Ter nonsense NM_001407949.1:c.31C>T NP_001394878.1:p.Gln11Ter nonsense NM_001407950.1:c.31C>T NP_001394879.1:p.Gln11Ter nonsense NM_001407951.1:c.31C>T NP_001394880.1:p.Gln11Ter nonsense NM_001407952.1:c.31C>T NP_001394881.1:p.Gln11Ter nonsense NM_001407953.1:c.31C>T NP_001394882.1:p.Gln11Ter nonsense NM_001407954.1:c.31C>T NP_001394883.1:p.Gln11Ter nonsense NM_001407955.1:c.31C>T NP_001394884.1:p.Gln11Ter nonsense NM_001407956.1:c.31C>T NP_001394885.1:p.Gln11Ter nonsense NM_001407957.1:c.31C>T NP_001394886.1:p.Gln11Ter nonsense NM_001407958.1:c.31C>T NP_001394887.1:p.Gln11Ter nonsense NM_001407959.1:c.-141C>T NM_001407960.1:c.-141C>T NM_001407962.1:c.-141C>T NM_001407963.1:c.-141C>T NM_001407964.1:c.100C>T NP_001394893.1:p.Gln34Ter nonsense NM_001407965.1:c.-141C>T NM_001407968.1:c.241C>T NP_001394897.1:p.Gln81Ter nonsense NM_001407969.1:c.241C>T NP_001394898.1:p.Gln81Ter nonsense NM_001407970.1:c.241C>T NP_001394899.1:p.Gln81Ter nonsense NM_001407971.1:c.241C>T NP_001394900.1:p.Gln81Ter nonsense NM_001407972.1:c.241C>T NP_001394901.1:p.Gln81Ter nonsense NM_001407973.1:c.241C>T NP_001394902.1:p.Gln81Ter nonsense NM_001407974.1:c.241C>T NP_001394903.1:p.Gln81Ter nonsense NM_001407975.1:c.241C>T NP_001394904.1:p.Gln81Ter nonsense NM_001407976.1:c.241C>T NP_001394905.1:p.Gln81Ter nonsense NM_001407977.1:c.241C>T NP_001394906.1:p.Gln81Ter nonsense NM_001407978.1:c.241C>T NP_001394907.1:p.Gln81Ter nonsense NM_001407979.1:c.241C>T NP_001394908.1:p.Gln81Ter nonsense NM_001407980.1:c.241C>T NP_001394909.1:p.Gln81Ter nonsense NM_001407981.1:c.241C>T NP_001394910.1:p.Gln81Ter nonsense NM_001407982.1:c.241C>T NP_001394911.1:p.Gln81Ter nonsense NM_001407983.1:c.241C>T NP_001394912.1:p.Gln81Ter nonsense NM_001407984.1:c.241C>T NP_001394913.1:p.Gln81Ter nonsense NM_001407985.1:c.241C>T NP_001394914.1:p.Gln81Ter nonsense NM_001407986.1:c.241C>T NP_001394915.1:p.Gln81Ter nonsense NM_001407990.1:c.241C>T NP_001394919.1:p.Gln81Ter nonsense NM_001407991.1:c.241C>T NP_001394920.1:p.Gln81Ter nonsense NM_001407992.1:c.241C>T NP_001394921.1:p.Gln81Ter nonsense NM_001407993.1:c.241C>T NP_001394922.1:p.Gln81Ter nonsense NM_001408392.1:c.241C>T NP_001395321.1:p.Gln81Ter nonsense NM_001408396.1:c.241C>T NP_001395325.1:p.Gln81Ter nonsense NM_001408397.1:c.241C>T NP_001395326.1:p.Gln81Ter nonsense NM_001408398.1:c.241C>T NP_001395327.1:p.Gln81Ter nonsense NM_001408399.1:c.241C>T NP_001395328.1:p.Gln81Ter nonsense NM_001408400.1:c.241C>T NP_001395329.1:p.Gln81Ter nonsense NM_001408401.1:c.241C>T NP_001395330.1:p.Gln81Ter nonsense NM_001408402.1:c.241C>T NP_001395331.1:p.Gln81Ter nonsense NM_001408403.1:c.241C>T NP_001395332.1:p.Gln81Ter nonsense NM_001408404.1:c.241C>T NP_001395333.1:p.Gln81Ter nonsense NM_001408406.1:c.241C>T NP_001395335.1:p.Gln81Ter nonsense NM_001408407.1:c.241C>T NP_001395336.1:p.Gln81Ter nonsense NM_001408408.1:c.241C>T NP_001395337.1:p.Gln81Ter nonsense NM_001408409.1:c.163C>T NP_001395338.1:p.Gln55Ter nonsense NM_001408410.1:c.100C>T NP_001395339.1:p.Gln34Ter nonsense NM_001408411.1:c.163C>T NP_001395340.1:p.Gln55Ter nonsense NM_001408412.1:c.163C>T NP_001395341.1:p.Gln55Ter nonsense NM_001408413.1:c.163C>T NP_001395342.1:p.Gln55Ter nonsense NM_001408414.1:c.163C>T NP_001395343.1:p.Gln55Ter nonsense NM_001408415.1:c.163C>T NP_001395344.1:p.Gln55Ter nonsense NM_001408416.1:c.163C>T NP_001395345.1:p.Gln55Ter nonsense NM_001408418.1:c.241C>T NP_001395347.1:p.Gln81Ter nonsense NM_001408419.1:c.241C>T NP_001395348.1:p.Gln81Ter nonsense NM_001408420.1:c.241C>T NP_001395349.1:p.Gln81Ter nonsense NM_001408421.1:c.241C>T NP_001395350.1:p.Gln81Ter nonsense NM_001408422.1:c.241C>T NP_001395351.1:p.Gln81Ter nonsense NM_001408423.1:c.241C>T NP_001395352.1:p.Gln81Ter nonsense NM_001408424.1:c.241C>T NP_001395353.1:p.Gln81Ter nonsense NM_001408425.1:c.241C>T NP_001395354.1:p.Gln81Ter nonsense NM_001408426.1:c.241C>T NP_001395355.1:p.Gln81Ter nonsense NM_001408427.1:c.241C>T NP_001395356.1:p.Gln81Ter nonsense NM_001408428.1:c.241C>T NP_001395357.1:p.Gln81Ter nonsense NM_001408429.1:c.241C>T NP_001395358.1:p.Gln81Ter nonsense NM_001408430.1:c.241C>T NP_001395359.1:p.Gln81Ter nonsense NM_001408431.1:c.241C>T NP_001395360.1:p.Gln81Ter nonsense NM_001408432.1:c.241C>T NP_001395361.1:p.Gln81Ter nonsense NM_001408433.1:c.241C>T NP_001395362.1:p.Gln81Ter nonsense NM_001408434.1:c.241C>T NP_001395363.1:p.Gln81Ter nonsense NM_001408435.1:c.241C>T NP_001395364.1:p.Gln81Ter nonsense NM_001408436.1:c.241C>T NP_001395365.1:p.Gln81Ter nonsense NM_001408437.1:c.241C>T NP_001395366.1:p.Gln81Ter nonsense NM_001408438.1:c.241C>T NP_001395367.1:p.Gln81Ter nonsense NM_001408439.1:c.241C>T NP_001395368.1:p.Gln81Ter nonsense NM_001408440.1:c.241C>T NP_001395369.1:p.Gln81Ter nonsense NM_001408441.1:c.241C>T NP_001395370.1:p.Gln81Ter nonsense NM_001408442.1:c.241C>T NP_001395371.1:p.Gln81Ter nonsense NM_001408443.1:c.241C>T NP_001395372.1:p.Gln81Ter nonsense NM_001408444.1:c.241C>T NP_001395373.1:p.Gln81Ter nonsense NM_001408445.1:c.241C>T NP_001395374.1:p.Gln81Ter nonsense NM_001408446.1:c.241C>T NP_001395375.1:p.Gln81Ter nonsense NM_001408447.1:c.241C>T NP_001395376.1:p.Gln81Ter nonsense NM_001408448.1:c.241C>T NP_001395377.1:p.Gln81Ter nonsense NM_001408450.1:c.241C>T NP_001395379.1:p.Gln81Ter nonsense NM_001408451.1:c.109C>T NP_001395380.1:p.Gln37Ter nonsense NM_001408452.1:c.100C>T NP_001395381.1:p.Gln34Ter nonsense NM_001408453.1:c.100C>T NP_001395382.1:p.Gln34Ter nonsense NM_001408454.1:c.100C>T NP_001395383.1:p.Gln34Ter nonsense NM_001408455.1:c.100C>T NP_001395384.1:p.Gln34Ter nonsense NM_001408456.1:c.100C>T NP_001395385.1:p.Gln34Ter nonsense NM_001408457.1:c.100C>T NP_001395386.1:p.Gln34Ter nonsense NM_001408458.1:c.100C>T NP_001395387.1:p.Gln34Ter nonsense NM_001408459.1:c.100C>T NP_001395388.1:p.Gln34Ter nonsense NM_001408460.1:c.100C>T NP_001395389.1:p.Gln34Ter nonsense NM_001408461.1:c.100C>T NP_001395390.1:p.Gln34Ter nonsense NM_001408462.1:c.100C>T NP_001395391.1:p.Gln34Ter nonsense NM_001408463.1:c.100C>T NP_001395392.1:p.Gln34Ter nonsense NM_001408464.1:c.100C>T NP_001395393.1:p.Gln34Ter nonsense NM_001408465.1:c.100C>T NP_001395394.1:p.Gln34Ter nonsense NM_001408466.1:c.100C>T NP_001395395.1:p.Gln34Ter nonsense NM_001408467.1:c.100C>T NP_001395396.1:p.Gln34Ter nonsense NM_001408468.1:c.100C>T NP_001395397.1:p.Gln34Ter nonsense NM_001408469.1:c.100C>T NP_001395398.1:p.Gln34Ter nonsense NM_001408470.1:c.100C>T NP_001395399.1:p.Gln34Ter nonsense NM_001408472.1:c.241C>T NP_001395401.1:p.Gln81Ter nonsense NM_001408473.1:c.241C>T NP_001395402.1:p.Gln81Ter nonsense NM_001408474.1:c.163C>T NP_001395403.1:p.Gln55Ter nonsense NM_001408475.1:c.163C>T NP_001395404.1:p.Gln55Ter nonsense NM_001408476.1:c.163C>T NP_001395405.1:p.Gln55Ter nonsense NM_001408478.1:c.31C>T NP_001395407.1:p.Gln11Ter nonsense NM_001408479.1:c.31C>T NP_001395408.1:p.Gln11Ter nonsense NM_001408480.1:c.31C>T NP_001395409.1:p.Gln11Ter nonsense NM_001408481.1:c.31C>T NP_001395410.1:p.Gln11Ter nonsense NM_001408482.1:c.31C>T NP_001395411.1:p.Gln11Ter nonsense NM_001408483.1:c.31C>T NP_001395412.1:p.Gln11Ter nonsense NM_001408484.1:c.31C>T NP_001395413.1:p.Gln11Ter nonsense NM_001408485.1:c.31C>T NP_001395414.1:p.Gln11Ter nonsense NM_001408489.1:c.31C>T NP_001395418.1:p.Gln11Ter nonsense NM_001408490.1:c.31C>T NP_001395419.1:p.Gln11Ter nonsense NM_001408491.1:c.31C>T NP_001395420.1:p.Gln11Ter nonsense NM_001408492.1:c.31C>T NP_001395421.1:p.Gln11Ter nonsense NM_001408493.1:c.31C>T NP_001395422.1:p.Gln11Ter nonsense NM_001408494.1:c.241C>T NP_001395423.1:p.Gln81Ter nonsense NM_001408495.1:c.241C>T NP_001395424.1:p.Gln81Ter nonsense NM_001408496.1:c.100C>T NP_001395425.1:p.Gln34Ter nonsense NM_001408497.1:c.100C>T NP_001395426.1:p.Gln34Ter nonsense NM_001408498.1:c.100C>T NP_001395427.1:p.Gln34Ter nonsense NM_001408499.1:c.100C>T NP_001395428.1:p.Gln34Ter nonsense NM_001408500.1:c.100C>T NP_001395429.1:p.Gln34Ter nonsense NM_001408501.1:c.100C>T NP_001395430.1:p.Gln34Ter nonsense NM_001408502.1:c.31C>T NP_001395431.1:p.Gln11Ter nonsense NM_001408503.1:c.100C>T NP_001395432.1:p.Gln34Ter nonsense NM_001408504.1:c.100C>T NP_001395433.1:p.Gln34Ter nonsense NM_001408505.1:c.100C>T NP_001395434.1:p.Gln34Ter nonsense NM_001408506.1:c.31C>T NP_001395435.1:p.Gln11Ter nonsense NM_001408507.1:c.31C>T NP_001395436.1:p.Gln11Ter nonsense NM_001408508.1:c.31C>T NP_001395437.1:p.Gln11Ter nonsense NM_001408509.1:c.31C>T NP_001395438.1:p.Gln11Ter nonsense NM_001408510.1:c.-141C>T NM_001408511.1:c.100C>T NP_001395440.1:p.Gln34Ter nonsense NM_001408512.1:c.-141C>T NM_001408513.1:c.31C>T NP_001395442.1:p.Gln11Ter nonsense NM_001408514.1:c.31C>T NP_001395443.1:p.Gln11Ter nonsense NM_007297.4:c.100C>T NP_009228.2:p.Gln34Ter nonsense NM_007298.4:c.241C>T NP_009229.2:p.Gln81Ter nonsense NM_007299.4:c.241C>T NP_009230.2:p.Gln81Ter nonsense NM_007300.4:c.241C>T NP_009231.2:p.Gln81Ter nonsense NM_007304.2:c.241C>T NP_009235.2:p.Gln81Ter nonsense NR_027676.2:n.421C>T non-coding transcript variant NC_000017.11:g.43104928G>A NC_000017.10:g.41256945G>A NG_005905.2:g.113056C>T LRG_292:g.113056C>T LRG_292t1:c.241C>T LRG_292p1:p.Gln81Ter U14680.1:n.360C>T - Protein change
- Q81*, Q34*, Q11*, Q55*, Q37*
- Other names
- -
- Canonical SPDI
- NC_000017.11:43104927:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
function_uncertain_variant; Sequence Ontology [ SO:0002220]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.241C>T, a NONSENSE variant, produced a function score of -1.3, corresponding to a functional classification of INTERMEDIATE. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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.
- -
- 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 (2) |
criteria provided, single submitter
|
Jul 8, 2021 | RCV000047834.21 | |
| Pathogenic (6) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000112105.17 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000763008.10 | |
| Pathogenic (1) |
no assertion criteria provided
|
Sep 6, 2000 | RCV000735472.9 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 19, 2022 | RCV001015488.11 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV001353463.10 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 15, 2023 | RCV003321493.8 |
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
(Sep 08, 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: SCV000299430.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Jul 01, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564299.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Oct 02, 2015)
|
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: SCV000325352.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004026823.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
|
|
Pathogenic
(Mar 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211771.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
|
Pathogenic
(Jul 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000075847.10
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been … (more)
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in a family affected with breast cancer or ovarian cancer (PMID: 15382066). This variant is also known as c.360C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54565). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln81*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. (less)
|
|
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Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000893453.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
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Pathogenic
(Aug 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001176327.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.Q81* pathogenic mutation (also known as c.241C>T), located in coding exon 4 of the BRCA1 gene, results from a C to T substitution at … (more)
The p.Q81* pathogenic mutation (also known as c.241C>T), located in coding exon 4 of the BRCA1 gene, results from a C to T substitution at nucleotide position 241. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This mutation has been reported in multiple families with hereditary breast and/or ovarian cancer (Oros KK et al. Int. J. Cancer 2004 Nov;112(3):411-9; Heramb C et al. Hered Cancer Clin Pract 2018 Jan;16:3; Arai M et al. J. Hum. Genet. 2018 Apr;63(4):447-457). Of note, this mutation is also designated as 360C>T in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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
(May 29, 2002)
|
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: SCV000144777.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Ethnicity/Population group: French Canadian
Observation 2:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European
|
|
|
Pathogenic
(Jan 31, 2014)
|
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: SCV000587041.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Pathogenic
(Sep 06, 2000)
|
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: SCV000863609.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
|
|
|
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: SCV000591253.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Gln81X variant was identified in 1 of 338 proband chromosomes (frequency: 0.003) from individuals or families with Breast and or Ovarian cancer (Oros, 2004). … (more)
The p.Gln81X variant was identified in 1 of 338 proband chromosomes (frequency: 0.003) from individuals or families with Breast and or Ovarian cancer (Oros, 2004). The variant was also identified in dbSNP (ID: rs80357350) “With pathogenic allele”, HGMD, ClinVar database (sighted by BIC and invitae), the BIC database (3X with class 5 clinical importance), and UMD (5X as a causal variant). The p.Gln81X variant leads to a premature stop codon at position 81, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
|
Brotman Baty Institute, University of Washington
Accession: SCV001238526.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
INTERMEDIATE:-1.29548719112128
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Comment:
Comment:
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in a family affected with breast cancer or ovarian cancer (PMID: 15382066). This variant is also known as c.360C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54565). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln81*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Comment:
The p.Q81* pathogenic mutation (also known as c.241C>T), located in coding exon 4 of the BRCA1 gene, results from a C to T substitution at nucleotide position 241. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This mutation has been reported in multiple families with hereditary breast and/or ovarian cancer (Oros KK et al. Int. J. Cancer 2004 Nov;112(3):411-9; Heramb C et al. Hered Cancer Clin Pract 2018 Jan;16:3; Arai M et al. J. Hum. Genet. 2018 Apr;63(4):447-457). Of note, this mutation is also designated as 360C>T in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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:
The p.Gln81X variant was identified in 1 of 338 proband chromosomes (frequency: 0.003) from individuals or families with Breast and or Ovarian cancer (Oros, 2004). The variant was also identified in dbSNP (ID: rs80357350) “With pathogenic allele”, HGMD, ClinVar database (sighted by BIC and invitae), the BIC database (3X with class 5 clinical importance), and UMD (5X as a causal variant). The p.Gln81X variant leads to a premature stop codon at position 81, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.
Germline Functional Evidence
| Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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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
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A brief description of the result of this method for this variant. |
Submitter
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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
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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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function_uncertain_variant
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001238526.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.241C>T, a NONSENSE variant, produced a function score of -1.3, corresponding to a functional classification of INTERMEDIATE. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.241C>T, a NONSENSE variant, produced a function score of -1.3, corresponding to a functional classification of INTERMEDIATE. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in a family affected with breast cancer or ovarian cancer (PMID: 15382066). This variant is also known as c.360C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54565). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln81*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Comment:
The p.Q81* pathogenic mutation (also known as c.241C>T), located in coding exon 4 of the BRCA1 gene, results from a C to T substitution at nucleotide position 241. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This mutation has been reported in multiple families with hereditary breast and/or ovarian cancer (Oros KK et al. Int. J. Cancer 2004 Nov;112(3):411-9; Heramb C et al. Hered Cancer Clin Pract 2018 Jan;16:3; Arai M et al. J. Hum. Genet. 2018 Apr;63(4):447-457). Of note, this mutation is also designated as 360C>T in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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:
The p.Gln81X variant was identified in 1 of 338 proband chromosomes (frequency: 0.003) from individuals or families with Breast and or Ovarian cancer (Oros, 2004). The variant was also identified in dbSNP (ID: rs80357350) “With pathogenic allele”, HGMD, ClinVar database (sighted by BIC and invitae), the BIC database (3X with class 5 clinical importance), and UMD (5X as a causal variant). The p.Gln81X variant leads to a premature stop codon at position 81, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| 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 |
| Significant proportion of breast and/or ovarian cancer families of French Canadian descent harbor 1 of 5 BRCA1 and BRCA2 mutations. | Oros KK | International journal of cancer | 2004 | PMID: 15382066 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs80357350 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
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.