IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000229
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2521C>T (p.Arg841Trp)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Aug 2015 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.2521C>T (p.Arg841Trp)
Variation ID: 17681 Accession: VCV000017681.91
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093010 (GRCh38) [ NCBI UCSC ] 17: 41245027 (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 4, 2013 Oct 20, 2024 Aug 10, 2015 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.2521C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Arg841Trp missense NM_001407571.1:c.2308C>T NP_001394500.1:p.Arg770Trp missense NM_001407581.1:c.2521C>T NP_001394510.1:p.Arg841Trp missense NM_001407582.1:c.2521C>T NP_001394511.1:p.Arg841Trp missense NM_001407583.1:c.2521C>T NP_001394512.1:p.Arg841Trp missense NM_001407585.1:c.2521C>T NP_001394514.1:p.Arg841Trp missense NM_001407587.1:c.2518C>T NP_001394516.1:p.Arg840Trp missense NM_001407590.1:c.2518C>T NP_001394519.1:p.Arg840Trp missense NM_001407591.1:c.2518C>T NP_001394520.1:p.Arg840Trp missense NM_001407593.1:c.2521C>T NP_001394522.1:p.Arg841Trp missense NM_001407594.1:c.2521C>T NP_001394523.1:p.Arg841Trp missense NM_001407596.1:c.2521C>T NP_001394525.1:p.Arg841Trp missense NM_001407597.1:c.2521C>T NP_001394526.1:p.Arg841Trp missense NM_001407598.1:c.2521C>T NP_001394527.1:p.Arg841Trp missense NM_001407602.1:c.2521C>T NP_001394531.1:p.Arg841Trp missense NM_001407603.1:c.2521C>T NP_001394532.1:p.Arg841Trp missense NM_001407605.1:c.2521C>T NP_001394534.1:p.Arg841Trp missense NM_001407610.1:c.2518C>T NP_001394539.1:p.Arg840Trp missense NM_001407611.1:c.2518C>T NP_001394540.1:p.Arg840Trp missense NM_001407612.1:c.2518C>T NP_001394541.1:p.Arg840Trp missense NM_001407613.1:c.2518C>T NP_001394542.1:p.Arg840Trp missense NM_001407614.1:c.2518C>T NP_001394543.1:p.Arg840Trp missense NM_001407615.1:c.2518C>T NP_001394544.1:p.Arg840Trp missense NM_001407616.1:c.2521C>T NP_001394545.1:p.Arg841Trp missense NM_001407617.1:c.2521C>T NP_001394546.1:p.Arg841Trp missense NM_001407618.1:c.2521C>T NP_001394547.1:p.Arg841Trp missense NM_001407619.1:c.2521C>T NP_001394548.1:p.Arg841Trp missense NM_001407620.1:c.2521C>T NP_001394549.1:p.Arg841Trp missense NM_001407621.1:c.2521C>T NP_001394550.1:p.Arg841Trp missense NM_001407622.1:c.2521C>T NP_001394551.1:p.Arg841Trp missense NM_001407623.1:c.2521C>T NP_001394552.1:p.Arg841Trp missense NM_001407624.1:c.2521C>T NP_001394553.1:p.Arg841Trp missense NM_001407625.1:c.2521C>T NP_001394554.1:p.Arg841Trp missense NM_001407626.1:c.2521C>T NP_001394555.1:p.Arg841Trp missense NM_001407627.1:c.2518C>T NP_001394556.1:p.Arg840Trp missense NM_001407628.1:c.2518C>T NP_001394557.1:p.Arg840Trp missense NM_001407629.1:c.2518C>T NP_001394558.1:p.Arg840Trp missense NM_001407630.1:c.2518C>T NP_001394559.1:p.Arg840Trp missense NM_001407631.1:c.2518C>T NP_001394560.1:p.Arg840Trp missense NM_001407632.1:c.2518C>T NP_001394561.1:p.Arg840Trp missense NM_001407633.1:c.2518C>T NP_001394562.1:p.Arg840Trp missense NM_001407634.1:c.2518C>T NP_001394563.1:p.Arg840Trp missense NM_001407635.1:c.2518C>T NP_001394564.1:p.Arg840Trp missense NM_001407636.1:c.2518C>T NP_001394565.1:p.Arg840Trp missense NM_001407637.1:c.2518C>T NP_001394566.1:p.Arg840Trp missense NM_001407638.1:c.2518C>T NP_001394567.1:p.Arg840Trp missense NM_001407639.1:c.2521C>T NP_001394568.1:p.Arg841Trp missense NM_001407640.1:c.2521C>T NP_001394569.1:p.Arg841Trp missense NM_001407641.1:c.2521C>T NP_001394570.1:p.Arg841Trp missense NM_001407642.1:c.2521C>T NP_001394571.1:p.Arg841Trp missense NM_001407644.1:c.2518C>T NP_001394573.1:p.Arg840Trp missense NM_001407645.1:c.2518C>T NP_001394574.1:p.Arg840Trp missense NM_001407646.1:c.2512C>T NP_001394575.1:p.Arg838Trp missense NM_001407647.1:c.2512C>T NP_001394576.1:p.Arg838Trp missense NM_001407648.1:c.2398C>T NP_001394577.1:p.Arg800Trp missense NM_001407649.1:c.2395C>T NP_001394578.1:p.Arg799Trp missense NM_001407652.1:c.2521C>T NP_001394581.1:p.Arg841Trp missense NM_001407653.1:c.2443C>T NP_001394582.1:p.Arg815Trp missense NM_001407654.1:c.2443C>T NP_001394583.1:p.Arg815Trp missense NM_001407655.1:c.2443C>T NP_001394584.1:p.Arg815Trp missense NM_001407656.1:c.2443C>T NP_001394585.1:p.Arg815Trp missense NM_001407657.1:c.2443C>T NP_001394586.1:p.Arg815Trp missense NM_001407658.1:c.2443C>T NP_001394587.1:p.Arg815Trp missense NM_001407659.1:c.2440C>T NP_001394588.1:p.Arg814Trp missense NM_001407660.1:c.2440C>T NP_001394589.1:p.Arg814Trp missense NM_001407661.1:c.2440C>T NP_001394590.1:p.Arg814Trp missense NM_001407662.1:c.2440C>T NP_001394591.1:p.Arg814Trp missense NM_001407663.1:c.2443C>T NP_001394592.1:p.Arg815Trp missense NM_001407664.1:c.2398C>T NP_001394593.1:p.Arg800Trp missense NM_001407665.1:c.2398C>T NP_001394594.1:p.Arg800Trp missense NM_001407666.1:c.2398C>T NP_001394595.1:p.Arg800Trp missense NM_001407667.1:c.2398C>T NP_001394596.1:p.Arg800Trp missense NM_001407668.1:c.2398C>T NP_001394597.1:p.Arg800Trp missense NM_001407669.1:c.2398C>T NP_001394598.1:p.Arg800Trp missense NM_001407670.1:c.2395C>T NP_001394599.1:p.Arg799Trp missense NM_001407671.1:c.2395C>T NP_001394600.1:p.Arg799Trp missense NM_001407672.1:c.2395C>T NP_001394601.1:p.Arg799Trp missense NM_001407673.1:c.2395C>T NP_001394602.1:p.Arg799Trp missense NM_001407674.1:c.2398C>T NP_001394603.1:p.Arg800Trp missense NM_001407675.1:c.2398C>T NP_001394604.1:p.Arg800Trp missense NM_001407676.1:c.2398C>T NP_001394605.1:p.Arg800Trp missense NM_001407677.1:c.2398C>T NP_001394606.1:p.Arg800Trp missense NM_001407678.1:c.2398C>T NP_001394607.1:p.Arg800Trp missense NM_001407679.1:c.2398C>T NP_001394608.1:p.Arg800Trp missense NM_001407680.1:c.2398C>T NP_001394609.1:p.Arg800Trp missense NM_001407681.1:c.2398C>T NP_001394610.1:p.Arg800Trp missense NM_001407682.1:c.2398C>T NP_001394611.1:p.Arg800Trp missense NM_001407683.1:c.2398C>T NP_001394612.1:p.Arg800Trp missense NM_001407684.1:c.2521C>T NP_001394613.1:p.Arg841Trp missense NM_001407685.1:c.2395C>T NP_001394614.1:p.Arg799Trp missense NM_001407686.1:c.2395C>T NP_001394615.1:p.Arg799Trp missense NM_001407687.1:c.2395C>T NP_001394616.1:p.Arg799Trp missense NM_001407688.1:c.2395C>T NP_001394617.1:p.Arg799Trp missense NM_001407689.1:c.2395C>T NP_001394618.1:p.Arg799Trp missense NM_001407690.1:c.2395C>T NP_001394619.1:p.Arg799Trp missense NM_001407691.1:c.2395C>T NP_001394620.1:p.Arg799Trp missense NM_001407692.1:c.2380C>T NP_001394621.1:p.Arg794Trp missense NM_001407694.1:c.2380C>T NP_001394623.1:p.Arg794Trp missense NM_001407695.1:c.2380C>T NP_001394624.1:p.Arg794Trp missense NM_001407696.1:c.2380C>T NP_001394625.1:p.Arg794Trp missense NM_001407697.1:c.2380C>T NP_001394626.1:p.Arg794Trp missense NM_001407698.1:c.2380C>T NP_001394627.1:p.Arg794Trp missense NM_001407724.1:c.2380C>T NP_001394653.1:p.Arg794Trp missense NM_001407725.1:c.2380C>T NP_001394654.1:p.Arg794Trp missense NM_001407726.1:c.2380C>T NP_001394655.1:p.Arg794Trp missense NM_001407727.1:c.2380C>T NP_001394656.1:p.Arg794Trp missense NM_001407728.1:c.2380C>T NP_001394657.1:p.Arg794Trp missense NM_001407729.1:c.2380C>T NP_001394658.1:p.Arg794Trp missense NM_001407730.1:c.2380C>T NP_001394659.1:p.Arg794Trp missense NM_001407731.1:c.2380C>T NP_001394660.1:p.Arg794Trp missense NM_001407732.1:c.2380C>T NP_001394661.1:p.Arg794Trp missense NM_001407733.1:c.2380C>T NP_001394662.1:p.Arg794Trp missense NM_001407734.1:c.2380C>T NP_001394663.1:p.Arg794Trp missense NM_001407735.1:c.2380C>T NP_001394664.1:p.Arg794Trp missense NM_001407736.1:c.2380C>T NP_001394665.1:p.Arg794Trp missense NM_001407737.1:c.2380C>T NP_001394666.1:p.Arg794Trp missense NM_001407738.1:c.2380C>T NP_001394667.1:p.Arg794Trp missense NM_001407739.1:c.2380C>T NP_001394668.1:p.Arg794Trp missense NM_001407740.1:c.2377C>T NP_001394669.1:p.Arg793Trp missense NM_001407741.1:c.2377C>T NP_001394670.1:p.Arg793Trp missense NM_001407742.1:c.2377C>T NP_001394671.1:p.Arg793Trp missense NM_001407743.1:c.2377C>T NP_001394672.1:p.Arg793Trp missense NM_001407744.1:c.2377C>T NP_001394673.1:p.Arg793Trp missense NM_001407745.1:c.2377C>T NP_001394674.1:p.Arg793Trp missense NM_001407746.1:c.2377C>T NP_001394675.1:p.Arg793Trp missense NM_001407747.1:c.2377C>T NP_001394676.1:p.Arg793Trp missense NM_001407748.1:c.2377C>T NP_001394677.1:p.Arg793Trp missense NM_001407749.1:c.2377C>T NP_001394678.1:p.Arg793Trp missense NM_001407750.1:c.2380C>T NP_001394679.1:p.Arg794Trp missense NM_001407751.1:c.2380C>T NP_001394680.1:p.Arg794Trp missense NM_001407752.1:c.2380C>T NP_001394681.1:p.Arg794Trp missense NM_001407838.1:c.2377C>T NP_001394767.1:p.Arg793Trp missense NM_001407839.1:c.2377C>T NP_001394768.1:p.Arg793Trp missense NM_001407841.1:c.2377C>T NP_001394770.1:p.Arg793Trp missense NM_001407842.1:c.2377C>T NP_001394771.1:p.Arg793Trp missense NM_001407843.1:c.2377C>T NP_001394772.1:p.Arg793Trp missense NM_001407844.1:c.2377C>T NP_001394773.1:p.Arg793Trp missense NM_001407845.1:c.2377C>T NP_001394774.1:p.Arg793Trp missense NM_001407846.1:c.2377C>T NP_001394775.1:p.Arg793Trp missense NM_001407847.1:c.2377C>T NP_001394776.1:p.Arg793Trp missense NM_001407848.1:c.2377C>T NP_001394777.1:p.Arg793Trp missense NM_001407849.1:c.2377C>T NP_001394778.1:p.Arg793Trp missense NM_001407850.1:c.2380C>T NP_001394779.1:p.Arg794Trp missense NM_001407851.1:c.2380C>T NP_001394780.1:p.Arg794Trp missense NM_001407852.1:c.2380C>T NP_001394781.1:p.Arg794Trp missense NM_001407853.1:c.2308C>T NP_001394782.1:p.Arg770Trp missense NM_001407854.1:c.2521C>T NP_001394783.1:p.Arg841Trp missense NM_001407858.1:c.2521C>T NP_001394787.1:p.Arg841Trp missense NM_001407859.1:c.2521C>T NP_001394788.1:p.Arg841Trp missense NM_001407860.1:c.2518C>T NP_001394789.1:p.Arg840Trp missense NM_001407861.1:c.2518C>T NP_001394790.1:p.Arg840Trp missense NM_001407862.1:c.2320C>T NP_001394791.1:p.Arg774Trp missense NM_001407863.1:c.2398C>T NP_001394792.1:p.Arg800Trp missense NM_001407874.1:c.2317C>T NP_001394803.1:p.Arg773Trp missense NM_001407875.1:c.2317C>T NP_001394804.1:p.Arg773Trp missense NM_001407879.1:c.2311C>T NP_001394808.1:p.Arg771Trp missense NM_001407881.1:c.2311C>T NP_001394810.1:p.Arg771Trp missense NM_001407882.1:c.2311C>T NP_001394811.1:p.Arg771Trp missense NM_001407884.1:c.2311C>T NP_001394813.1:p.Arg771Trp missense NM_001407885.1:c.2311C>T NP_001394814.1:p.Arg771Trp missense NM_001407886.1:c.2311C>T NP_001394815.1:p.Arg771Trp missense NM_001407887.1:c.2311C>T NP_001394816.1:p.Arg771Trp missense NM_001407889.1:c.2311C>T NP_001394818.1:p.Arg771Trp missense NM_001407894.1:c.2308C>T NP_001394823.1:p.Arg770Trp missense NM_001407895.1:c.2308C>T NP_001394824.1:p.Arg770Trp missense NM_001407896.1:c.2308C>T NP_001394825.1:p.Arg770Trp missense NM_001407897.1:c.2308C>T NP_001394826.1:p.Arg770Trp missense NM_001407898.1:c.2308C>T NP_001394827.1:p.Arg770Trp missense NM_001407899.1:c.2308C>T NP_001394828.1:p.Arg770Trp missense NM_001407900.1:c.2311C>T NP_001394829.1:p.Arg771Trp missense NM_001407902.1:c.2311C>T NP_001394831.1:p.Arg771Trp missense NM_001407904.1:c.2311C>T NP_001394833.1:p.Arg771Trp missense NM_001407906.1:c.2311C>T NP_001394835.1:p.Arg771Trp missense NM_001407907.1:c.2311C>T NP_001394836.1:p.Arg771Trp missense NM_001407908.1:c.2311C>T NP_001394837.1:p.Arg771Trp missense NM_001407909.1:c.2311C>T NP_001394838.1:p.Arg771Trp missense NM_001407910.1:c.2311C>T NP_001394839.1:p.Arg771Trp missense NM_001407915.1:c.2308C>T NP_001394844.1:p.Arg770Trp missense NM_001407916.1:c.2308C>T NP_001394845.1:p.Arg770Trp missense NM_001407917.1:c.2308C>T NP_001394846.1:p.Arg770Trp missense NM_001407918.1:c.2308C>T NP_001394847.1:p.Arg770Trp missense NM_001407919.1:c.2398C>T NP_001394848.1:p.Arg800Trp missense NM_001407920.1:c.2257C>T NP_001394849.1:p.Arg753Trp missense NM_001407921.1:c.2257C>T NP_001394850.1:p.Arg753Trp missense NM_001407922.1:c.2257C>T NP_001394851.1:p.Arg753Trp missense NM_001407923.1:c.2257C>T NP_001394852.1:p.Arg753Trp missense NM_001407924.1:c.2257C>T NP_001394853.1:p.Arg753Trp missense NM_001407925.1:c.2257C>T NP_001394854.1:p.Arg753Trp missense NM_001407926.1:c.2257C>T NP_001394855.1:p.Arg753Trp missense NM_001407927.1:c.2257C>T NP_001394856.1:p.Arg753Trp missense NM_001407928.1:c.2257C>T NP_001394857.1:p.Arg753Trp missense NM_001407929.1:c.2257C>T NP_001394858.1:p.Arg753Trp missense NM_001407930.1:c.2254C>T NP_001394859.1:p.Arg752Trp missense NM_001407931.1:c.2254C>T NP_001394860.1:p.Arg752Trp missense NM_001407932.1:c.2254C>T NP_001394861.1:p.Arg752Trp missense NM_001407933.1:c.2257C>T NP_001394862.1:p.Arg753Trp missense NM_001407934.1:c.2254C>T NP_001394863.1:p.Arg752Trp missense NM_001407935.1:c.2257C>T NP_001394864.1:p.Arg753Trp missense NM_001407936.1:c.2254C>T NP_001394865.1:p.Arg752Trp missense NM_001407937.1:c.2398C>T NP_001394866.1:p.Arg800Trp missense NM_001407938.1:c.2398C>T NP_001394867.1:p.Arg800Trp missense NM_001407939.1:c.2398C>T NP_001394868.1:p.Arg800Trp missense NM_001407940.1:c.2395C>T NP_001394869.1:p.Arg799Trp missense NM_001407941.1:c.2395C>T NP_001394870.1:p.Arg799Trp missense NM_001407942.1:c.2380C>T NP_001394871.1:p.Arg794Trp missense NM_001407943.1:c.2377C>T NP_001394872.1:p.Arg793Trp missense NM_001407944.1:c.2380C>T NP_001394873.1:p.Arg794Trp missense NM_001407945.1:c.2380C>T NP_001394874.1:p.Arg794Trp missense NM_001407946.1:c.2188C>T NP_001394875.1:p.Arg730Trp missense NM_001407947.1:c.2188C>T NP_001394876.1:p.Arg730Trp missense NM_001407948.1:c.2188C>T NP_001394877.1:p.Arg730Trp missense NM_001407949.1:c.2188C>T NP_001394878.1:p.Arg730Trp missense NM_001407950.1:c.2188C>T NP_001394879.1:p.Arg730Trp missense NM_001407951.1:c.2188C>T NP_001394880.1:p.Arg730Trp missense NM_001407952.1:c.2188C>T NP_001394881.1:p.Arg730Trp missense NM_001407953.1:c.2188C>T NP_001394882.1:p.Arg730Trp missense NM_001407954.1:c.2185C>T NP_001394883.1:p.Arg729Trp missense NM_001407955.1:c.2185C>T NP_001394884.1:p.Arg729Trp missense NM_001407956.1:c.2185C>T NP_001394885.1:p.Arg729Trp missense NM_001407957.1:c.2188C>T NP_001394886.1:p.Arg730Trp missense NM_001407958.1:c.2185C>T NP_001394887.1:p.Arg729Trp missense NM_001407959.1:c.2140C>T NP_001394888.1:p.Arg714Trp missense NM_001407960.1:c.2140C>T NP_001394889.1:p.Arg714Trp missense NM_001407962.1:c.2137C>T NP_001394891.1:p.Arg713Trp missense NM_001407963.1:c.2140C>T NP_001394892.1:p.Arg714Trp missense NM_001407964.1:c.2377C>T NP_001394893.1:p.Arg793Trp missense NM_001407965.1:c.2017C>T NP_001394894.1:p.Arg673Trp missense NM_001407966.1:c.1633C>T NP_001394895.1:p.Arg545Trp missense NM_001407967.1:c.1633C>T NP_001394896.1:p.Arg545Trp missense NM_001407968.1:c.788-871C>T intron variant NM_001407969.1:c.788-871C>T intron variant NM_001407970.1:c.787+1734C>T intron variant NM_001407971.1:c.787+1734C>T intron variant NM_001407972.1:c.784+1734C>T intron variant NM_001407973.1:c.787+1734C>T intron variant NM_001407974.1:c.787+1734C>T intron variant NM_001407975.1:c.787+1734C>T intron variant NM_001407976.1:c.787+1734C>T intron variant NM_001407977.1:c.787+1734C>T intron variant NM_001407978.1:c.787+1734C>T intron variant NM_001407979.1:c.787+1734C>T intron variant NM_001407980.1:c.787+1734C>T intron variant NM_001407981.1:c.787+1734C>T intron variant NM_001407982.1:c.787+1734C>T intron variant NM_001407983.1:c.787+1734C>T intron variant NM_001407984.1:c.784+1734C>T intron variant NM_001407985.1:c.784+1734C>T intron variant NM_001407986.1:c.784+1734C>T intron variant NM_001407990.1:c.787+1734C>T intron variant NM_001407991.1:c.784+1734C>T intron variant NM_001407992.1:c.784+1734C>T intron variant NM_001407993.1:c.787+1734C>T intron variant NM_001408392.1:c.784+1734C>T intron variant NM_001408396.1:c.784+1734C>T intron variant NM_001408397.1:c.784+1734C>T intron variant NM_001408398.1:c.784+1734C>T intron variant NM_001408399.1:c.784+1734C>T intron variant NM_001408400.1:c.784+1734C>T intron variant NM_001408401.1:c.784+1734C>T intron variant NM_001408402.1:c.784+1734C>T intron variant NM_001408403.1:c.787+1734C>T intron variant NM_001408404.1:c.787+1734C>T intron variant NM_001408406.1:c.790+1731C>T intron variant NM_001408407.1:c.784+1734C>T intron variant NM_001408408.1:c.778+1734C>T intron variant NM_001408409.1:c.709+1734C>T intron variant NM_001408410.1:c.646+1734C>T intron variant NM_001408411.1:c.709+1734C>T intron variant NM_001408412.1:c.709+1734C>T intron variant NM_001408413.1:c.706+1734C>T intron variant NM_001408414.1:c.709+1734C>T intron variant NM_001408415.1:c.709+1734C>T intron variant NM_001408416.1:c.706+1734C>T intron variant NM_001408418.1:c.671-1978C>T intron variant NM_001408419.1:c.671-1978C>T intron variant NM_001408420.1:c.671-1978C>T intron variant NM_001408421.1:c.668-1978C>T intron variant NM_001408422.1:c.671-1978C>T intron variant NM_001408423.1:c.671-1978C>T intron variant NM_001408424.1:c.668-1978C>T intron variant NM_001408425.1:c.664+1734C>T intron variant NM_001408426.1:c.664+1734C>T intron variant NM_001408427.1:c.664+1734C>T intron variant NM_001408428.1:c.664+1734C>T intron variant NM_001408429.1:c.664+1734C>T intron variant NM_001408430.1:c.664+1734C>T intron variant NM_001408431.1:c.668-1978C>T intron variant NM_001408432.1:c.661+1734C>T intron variant NM_001408433.1:c.661+1734C>T intron variant NM_001408434.1:c.661+1734C>T intron variant NM_001408435.1:c.661+1734C>T intron variant NM_001408436.1:c.664+1734C>T intron variant NM_001408437.1:c.664+1734C>T intron variant NM_001408438.1:c.664+1734C>T intron variant NM_001408439.1:c.664+1734C>T intron variant NM_001408440.1:c.664+1734C>T intron variant NM_001408441.1:c.664+1734C>T intron variant NM_001408442.1:c.664+1734C>T intron variant NM_001408443.1:c.664+1734C>T intron variant NM_001408444.1:c.664+1734C>T intron variant NM_001408445.1:c.661+1734C>T intron variant NM_001408446.1:c.661+1734C>T intron variant NM_001408447.1:c.661+1734C>T intron variant NM_001408448.1:c.661+1734C>T intron variant NM_001408450.1:c.661+1734C>T intron variant NM_001408451.1:c.652+1734C>T intron variant NM_001408452.1:c.646+1734C>T intron variant NM_001408453.1:c.646+1734C>T intron variant NM_001408454.1:c.646+1734C>T intron variant NM_001408455.1:c.646+1734C>T intron variant NM_001408456.1:c.646+1734C>T intron variant NM_001408457.1:c.646+1734C>T intron variant NM_001408458.1:c.646+1734C>T intron variant NM_001408459.1:c.646+1734C>T intron variant NM_001408460.1:c.646+1734C>T intron variant NM_001408461.1:c.646+1734C>T intron variant NM_001408462.1:c.643+1734C>T intron variant NM_001408463.1:c.643+1734C>T intron variant NM_001408464.1:c.643+1734C>T intron variant NM_001408465.1:c.643+1734C>T intron variant NM_001408466.1:c.646+1734C>T intron variant NM_001408467.1:c.646+1734C>T intron variant NM_001408468.1:c.643+1734C>T intron variant NM_001408469.1:c.646+1734C>T intron variant NM_001408470.1:c.643+1734C>T intron variant NM_001408472.1:c.787+1734C>T intron variant NM_001408473.1:c.784+1734C>T intron variant NM_001408474.1:c.586+1734C>T intron variant NM_001408475.1:c.583+1734C>T intron variant NM_001408476.1:c.586+1734C>T intron variant NM_001408478.1:c.577+1734C>T intron variant NM_001408479.1:c.577+1734C>T intron variant NM_001408480.1:c.577+1734C>T intron variant NM_001408481.1:c.577+1734C>T intron variant NM_001408482.1:c.577+1734C>T intron variant NM_001408483.1:c.577+1734C>T intron variant NM_001408484.1:c.577+1734C>T intron variant NM_001408485.1:c.577+1734C>T intron variant NM_001408489.1:c.577+1734C>T intron variant NM_001408490.1:c.574+1734C>T intron variant NM_001408491.1:c.574+1734C>T intron variant NM_001408492.1:c.577+1734C>T intron variant NM_001408493.1:c.574+1734C>T intron variant NM_001408494.1:c.548-1978C>T intron variant NM_001408495.1:c.545-1978C>T intron variant NM_001408496.1:c.523+1734C>T intron variant NM_001408497.1:c.523+1734C>T intron variant NM_001408498.1:c.523+1734C>T intron variant NM_001408499.1:c.523+1734C>T intron variant NM_001408500.1:c.523+1734C>T intron variant NM_001408501.1:c.523+1734C>T intron variant NM_001408502.1:c.454+1734C>T intron variant NM_001408503.1:c.520+1734C>T intron variant NM_001408504.1:c.520+1734C>T intron variant NM_001408505.1:c.520+1734C>T intron variant NM_001408506.1:c.461-1978C>T intron variant NM_001408507.1:c.461-1978C>T intron variant NM_001408508.1:c.451+1734C>T intron variant NM_001408509.1:c.451+1734C>T intron variant NM_001408510.1:c.406+1734C>T intron variant NM_001408511.1:c.404-1978C>T intron variant NM_001408512.1:c.283+1734C>T intron variant NM_001408513.1:c.577+1734C>T intron variant NM_001408514.1:c.577+1734C>T intron variant NM_007297.4:c.2380C>T NP_009228.2:p.Arg794Trp missense NM_007298.4:c.787+1734C>T intron variant NM_007299.4:c.787+1734C>T intron variant NM_007300.4:c.2521C>T NP_009231.2:p.Arg841Trp missense NR_027676.1:n.2657C>T NC_000017.11:g.43093010G>A NC_000017.10:g.41245027G>A NG_005905.2:g.124974C>T LRG_292:g.124974C>T LRG_292t1:c.2521C>T LRG_292p1:p.Arg841Trp P38398:p.Arg841Trp U14680.1:n.2640C>T - Protein change
- R841W, R794W, R840W, R673W, R730W, R752W, R799W, R838W, R545W, R713W, R770W, R773W, R814W, R815W, R729W, R753W, R771W, R800W, R714W, R774W, R793W
- Other names
-
p.R841W:CGG>TGG
2640C>T
- Canonical SPDI
- NC_000017.11:43093009:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00220 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00137
Trans-Omics for Precision Medicine (TOPMed) 0.00145
The Genome Aggregation Database (gnomAD), exomes 0.00167
Exome Aggregation Consortium (ExAC) 0.00172
1000 Genomes Project 30x 0.00219
1000 Genomes Project 0.00220
- 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. |
|---|---|---|---|---|
| Benign (14) |
reviewed by expert panel
|
Aug 10, 2015 | RCV000019251.30 | |
| Benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2024 | RCV000034733.42 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000047867.28 | |
| Benign/Likely benign (11) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000120283.43 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jul 15, 2020 | RCV000162566.15 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 8, 2019 | RCV000457953.11 | |
| Benign (1) |
criteria provided, single submitter
|
Mar 14, 2019 | RCV001170820.10 | |
| Benign (1) |
criteria provided, single submitter
|
Mar 22, 2022 | RCV002490393.8 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Aug 10, 2015)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000244321.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on … (more)
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000229 (less)
|
|
|
Benign
(Apr 21, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000267702.1
First in ClinVar: Nov 14, 2015 Last updated: Nov 14, 2015 |
Tissue: Blood
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000311791.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Feb 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000540974.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
|
|
|
Benign
(Oct 09, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743415.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Benign
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744655.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Likely benign
(Nov 08, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369371.2
First in ClinVar: Jul 06, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BP1,BP4,BP6.
|
|
|
Benign
(Mar 22, 2022)
|
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: SCV002802929.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Aug 02, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156725.5
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(Mar 29, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538437.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.2% (145/66714) European chromosomes; ClinVar: 7 labs classify as benign (less)
Method: Genome/Exome Filtration
|
|
|
Benign
(Apr 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586885.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Benign
(Nov 04, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167280.11
First in ClinVar: Jun 23, 2014 Last updated: Dec 02, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Oct 13, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000336440.4
First in ClinVar: Dec 06, 2016 Last updated: Sep 22, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Likely benign
(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: SCV001140573.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
|
Likely benign
(Jan 30, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001280881.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Benign
(Mar 14, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333438.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
|
|
|
Likely benign
(Nov 01, 2021)
|
criteria provided, single submitter
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515192.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
|
|
|
Benign
(Jul 15, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002538132.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Likely benign
(Dec 13, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000683041.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Benign
(Oct 06, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494310.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
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Likely benign
(Feb 18, 2014)
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criteria provided, single submitter
Method: literature only
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Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000154021.2
First in ClinVar: Jun 04, 2014 Last updated: Dec 24, 2022 |
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Likely benign
(Nov 06, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary Breast and Ovarian Cancer
Affected status: unknown
Allele origin:
unknown
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000297225.3
First in ClinVar: Jan 31, 2016 Last updated: Dec 24, 2022 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016783.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551017.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Benign
(Mar 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600292.5
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000075880.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
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Benign
(Jul 14, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000212979.6
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(Jul 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002545930.16
First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024 |
Comment:
BRCA1: BP4, BS1, BS2
Number of individuals with the variant: 8
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Uncertain significance
(Nov 01, 2012)
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000039539.3
First in ClinVar: Apr 04, 2013 Last updated: Nov 14, 2015 |
Comment on evidence:
This variant, formerly titled BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1, has been reclassified based on the findings of Millot et al. (2012). Barker et al. … (more)
This variant, formerly titled BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1, has been reclassified based on the findings of Millot et al. (2012). Barker et al. (1996) reported an arg841-to-trp (R814W) mutation in the BRCA1 gene as a common mutation identified in patients with breast-ovarian cancer (604370). Functional assays used to assess the impact of the R814W variant indicated that R814W is a class 1 variant (not pathogenic or of no clinical significance), according to the International Agency for Research on Cancer (IARC) class system (Millot et al., 2012). (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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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: SCV001905820.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951674.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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no known pathogenicity
(Jul 13, 2012)
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no assertion criteria provided
Method: research
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not provided
Affected status: no
Allele origin:
germline
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043175.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Benign.
Number of individuals with the variant: 3
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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Uncertain significance
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144466.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 55
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Austria
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Spain
Observation 4:
Number of individuals with the variant: 4
Geographic origin: Western European
Observation 5:
Number of individuals with the variant: 1
Geographic origin: Western European, Ashkenazi
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: African American
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Central/Eastern European
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Near Eastern
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Carribean
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: France
Observation 12:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 13:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Geographic origin: Spain
Observation 14:
Number of individuals with the variant: 2
Ethnicity/Population group: Central/Eastern European
Observation 15:
Number of individuals with the variant: 2
Ethnicity/Population group: Latin American, Caribbean
Observation 16:
Number of individuals with the variant: 1
Ethnicity/Population group: Native American
Observation 17:
Number of individuals with the variant: 41
Ethnicity/Population group: Western European
Observation 18:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, English, Irish
Observation 19:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Latin American, Caribbean
Observation 20:
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
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Benign
(Mar 01, 2011)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000053650.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Likely benign
(May 01, 2016)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: no
Allele origin:
germline
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Department of Medical Genetics, University Hospital of North Norway
Accession: SCV000301432.1
First in ClinVar: Nov 14, 2015 Last updated: Nov 14, 2015 |
Number of individuals with the variant: 1
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733641.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Benign
(Mar 08, 2017)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778755.1
First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015 |
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Likely benign
(Oct 10, 2017)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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True Health Diagnostics
Accession: SCV000787898.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591392.2 First in ClinVar: Aug 27, 2017 Last updated: Jan 26, 2021 |
Comment:
The p.Arg841Trp variant has been previously reported in 16/8958 proband chromosomes (frequency: 0.002) in individuals with breast or ovarian cancer, however, no controls were included … (more)
The p.Arg841Trp variant has been previously reported in 16/8958 proband chromosomes (frequency: 0.002) in individuals with breast or ovarian cancer, however, no controls were included in these studies (Barker 1996, Borg 2010, Diez 2003, Janezic 1999, Pal 2004, Shattuck-Eidens 1997). The variant was also listed in the dbSNP database as having an average heterozygosity of 0.006+/-0.056 (ID#:rs1800709), increasing the likelihood this variant does not have clinical significance. The p.Arg841 residue is not conserved in mammals or lower organisms; however, computational analyses (SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. There are also numerous studies in the literature which have attempted to classify this variant using different modeling appoaches but the effect of this variant on protein function remains undetermined (Burk Herrick 2006, Chenevix-Trench 2006, Goldgar 2004, Fleming 2003, Lindor 2011, Petersen 1998). Notably, this variant was reported in the UMD database, 54 times and in 6 individuals with a second pathogenic variant in either the BRCA1 or BRCA2 genes, increasing the likelihood the p.Arg841Trp variant is benign. It is also reported 114 times in the BIC database with unknown clinical consequence, although this high frequency might suggest it is a common benign polymorphism. Finally, this variant was reported by Myriad as a common polymorphism. In summary, based on the above information, this variant is classified as benign. (less)
Number of individuals with the variant: 12
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001800207.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004244087.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084435.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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Comment:
Comment:
This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BP1,BP4,BP6.
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.2% (145/66714) European chromosomes; ClinVar: 7 labs classify as benign
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
BRCA1: BP4, BS1, BS2
Comment:
Converted during submission to Benign.
Comment:
The p.Arg841Trp variant has been previously reported in 16/8958 proband chromosomes (frequency: 0.002) in individuals with breast or ovarian cancer, however, no controls were included in these studies (Barker 1996, Borg 2010, Diez 2003, Janezic 1999, Pal 2004, Shattuck-Eidens 1997). The variant was also listed in the dbSNP database as having an average heterozygosity of 0.006+/-0.056 (ID#:rs1800709), increasing the likelihood this variant does not have clinical significance. The p.Arg841 residue is not conserved in mammals or lower organisms; however, computational analyses (SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. There are also numerous studies in the literature which have attempted to classify this variant using different modeling appoaches but the effect of this variant on protein function remains undetermined (Burk Herrick 2006, Chenevix-Trench 2006, Goldgar 2004, Fleming 2003, Lindor 2011, Petersen 1998). Notably, this variant was reported in the UMD database, 54 times and in 6 individuals with a second pathogenic variant in either the BRCA1 or BRCA2 genes, increasing the likelihood the p.Arg841Trp variant is benign. It is also reported 114 times in the BIC database with unknown clinical consequence, although this high frequency might suggest it is a common benign polymorphism. Finally, this variant was reported by Myriad as a common polymorphism. In summary, based on the above information, this variant is classified as benign.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000229
Comment:
This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BP1,BP4,BP6.
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.2% (145/66714) European chromosomes; ClinVar: 7 labs classify as benign
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
BRCA1: BP4, BS1, BS2
Comment:
Converted during submission to Benign.
Comment:
The p.Arg841Trp variant has been previously reported in 16/8958 proband chromosomes (frequency: 0.002) in individuals with breast or ovarian cancer, however, no controls were included in these studies (Barker 1996, Borg 2010, Diez 2003, Janezic 1999, Pal 2004, Shattuck-Eidens 1997). The variant was also listed in the dbSNP database as having an average heterozygosity of 0.006+/-0.056 (ID#:rs1800709), increasing the likelihood this variant does not have clinical significance. The p.Arg841 residue is not conserved in mammals or lower organisms; however, computational analyses (SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. There are also numerous studies in the literature which have attempted to classify this variant using different modeling appoaches but the effect of this variant on protein function remains undetermined (Burk Herrick 2006, Chenevix-Trench 2006, Goldgar 2004, Fleming 2003, Lindor 2011, Petersen 1998). Notably, this variant was reported in the UMD database, 54 times and in 6 individuals with a second pathogenic variant in either the BRCA1 or BRCA2 genes, increasing the likelihood the p.Arg841Trp variant is benign. It is also reported 114 times in the BIC database with unknown clinical consequence, although this high frequency might suggest it is a common benign polymorphism. Finally, this variant was reported by Myriad as a common polymorphism. In summary, based on the above information, this variant is classified as benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service. | Matta BP | Scientific reports | 2022 | PMID: 36329109 |
| Breast cancer risks associated with missense variants in breast cancer susceptibility genes. | Dorling L | Genome medicine | 2022 | PMID: 35585550 |
| Prevalence of BRCA1 and BRCA2 pathogenic sequence variants in ovarian cancer patients in the Gulf region: the PREDICT study. | Azribi F | BMC cancer | 2021 | PMID: 34930165 |
| Next-generation sequencing of BRCA1 and BRCA2 genes in Moroccan prostate cancer patients with positive family history. | Salmi F | PloS one | 2021 | PMID: 34242281 |
| BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer. | Shimelis H | Cancer research | 2017 | PMID: 28283652 |
| The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry. | Peixoto A | Clinical genetics | 2015 | PMID: 24916970 |
| A guide for functional analysis of BRCA1 variants of uncertain significance. | Millot GA | Human mutation | 2012 | PMID: 22753008 |
| Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
| A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). | Lindor NM | Human mutation | 2012 | PMID: 21990134 |
| A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes. | Hondow HL | BMC cancer | 2011 | PMID: 21702907 |
| Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling. | Capanu M | Genetic epidemiology | 2011 | PMID: 21520273 |
| Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia. | Konecny M | Breast cancer research and treatment | 2011 | PMID: 21203900 |
| 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 |
| Incorporating the amino acid properties to predict the significance of missense mutations. | Lee TC | Amino acids | 2008 | PMID: 18415037 |
| Classification of missense variants of unknown significance in BRCA1 based on clinical and tumor information. | Osorio A | Human mutation | 2007 | PMID: 17279547 |
| Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans. | Burk-Herrick A | Mammalian genome : official journal of the International Mammalian Genome Society | 2006 | PMID: 16518693 |
| Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. | Chenevix-Trench G | Cancer research | 2006 | PMID: 16489001 |
| Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. | Tavtigian SV | Journal of medical genetics | 2006 | PMID: 16014699 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| BRCA1 and BRCA2 mutations in a study of African American breast cancer patients. | Pal T | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2004 | PMID: 15533909 |
| Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. | Goldgar DE | American journal of human genetics | 2004 | PMID: 15290653 |
| Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. | Díez O | Human mutation | 2003 | PMID: 12955716 |
| A full-likelihood method for the evaluation of causality of sequence variants from family data. | Thompson D | American journal of human genetics | 2003 | PMID: 12900794 |
| Understanding missense mutations in the BRCA1 gene: an evolutionary approach. | Fleming MA | Proceedings of the National Academy of Sciences of the United States of America | 2003 | PMID: 12531920 |
| A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene. | Dong J | Human genetics | 1998 | PMID: 9760198 |
| Missense mutations in disease genes: a Bayesian approach to evaluate causality. | Petersen GM | American journal of human genetics | 1998 | PMID: 9585599 |
| BRCA1 R841W: a strong candidate for a common mutation with moderate phenotype. | Barker DF | Genetic epidemiology | 1996 | PMID: 8968716 |
| Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. | Durocher F | Human molecular genetics | 1996 | PMID: 8776600 |
| http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA1&action=search_all&search_Variant%2FDNA=c.2521C%3ET | - | - | - | - |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA1 | - | - | - | - |
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Text-mined citations for rs1800709 ...
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.