ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3914A>T (p.Asp1305Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(4); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.3914A>T (p.Asp1305Val)
Variation ID: 96920 Accession: VCV000096920.22
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091617 (GRCh38) [ NCBI UCSC ] 17: 41243634 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 27, 2014 May 1, 2024 Nov 2, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.3914A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Asp1305Val missense NM_001407571.1:c.3701A>T NP_001394500.1:p.Asp1234Val missense NM_001407581.1:c.3914A>T NP_001394510.1:p.Asp1305Val missense NM_001407582.1:c.3914A>T NP_001394511.1:p.Asp1305Val missense NM_001407583.1:c.3914A>T NP_001394512.1:p.Asp1305Val missense NM_001407585.1:c.3914A>T NP_001394514.1:p.Asp1305Val missense NM_001407587.1:c.3911A>T NP_001394516.1:p.Asp1304Val missense NM_001407590.1:c.3911A>T NP_001394519.1:p.Asp1304Val missense NM_001407591.1:c.3911A>T NP_001394520.1:p.Asp1304Val missense NM_001407593.1:c.3914A>T NP_001394522.1:p.Asp1305Val missense NM_001407594.1:c.3914A>T NP_001394523.1:p.Asp1305Val missense NM_001407596.1:c.3914A>T NP_001394525.1:p.Asp1305Val missense NM_001407597.1:c.3914A>T NP_001394526.1:p.Asp1305Val missense NM_001407598.1:c.3914A>T NP_001394527.1:p.Asp1305Val missense NM_001407602.1:c.3914A>T NP_001394531.1:p.Asp1305Val missense NM_001407603.1:c.3914A>T NP_001394532.1:p.Asp1305Val missense NM_001407605.1:c.3914A>T NP_001394534.1:p.Asp1305Val missense NM_001407610.1:c.3911A>T NP_001394539.1:p.Asp1304Val missense NM_001407611.1:c.3911A>T NP_001394540.1:p.Asp1304Val missense NM_001407612.1:c.3911A>T NP_001394541.1:p.Asp1304Val missense NM_001407613.1:c.3911A>T NP_001394542.1:p.Asp1304Val missense NM_001407614.1:c.3911A>T NP_001394543.1:p.Asp1304Val missense NM_001407615.1:c.3911A>T NP_001394544.1:p.Asp1304Val missense NM_001407616.1:c.3914A>T NP_001394545.1:p.Asp1305Val missense NM_001407617.1:c.3914A>T NP_001394546.1:p.Asp1305Val missense NM_001407618.1:c.3914A>T NP_001394547.1:p.Asp1305Val missense NM_001407619.1:c.3914A>T NP_001394548.1:p.Asp1305Val missense NM_001407620.1:c.3914A>T NP_001394549.1:p.Asp1305Val missense NM_001407621.1:c.3914A>T NP_001394550.1:p.Asp1305Val missense NM_001407622.1:c.3914A>T NP_001394551.1:p.Asp1305Val missense NM_001407623.1:c.3914A>T NP_001394552.1:p.Asp1305Val missense NM_001407624.1:c.3914A>T NP_001394553.1:p.Asp1305Val missense NM_001407625.1:c.3914A>T NP_001394554.1:p.Asp1305Val missense NM_001407626.1:c.3914A>T NP_001394555.1:p.Asp1305Val missense NM_001407627.1:c.3911A>T NP_001394556.1:p.Asp1304Val missense NM_001407628.1:c.3911A>T NP_001394557.1:p.Asp1304Val missense NM_001407629.1:c.3911A>T NP_001394558.1:p.Asp1304Val missense NM_001407630.1:c.3911A>T NP_001394559.1:p.Asp1304Val missense NM_001407631.1:c.3911A>T NP_001394560.1:p.Asp1304Val missense NM_001407632.1:c.3911A>T NP_001394561.1:p.Asp1304Val missense NM_001407633.1:c.3911A>T NP_001394562.1:p.Asp1304Val missense NM_001407634.1:c.3911A>T NP_001394563.1:p.Asp1304Val missense NM_001407635.1:c.3911A>T NP_001394564.1:p.Asp1304Val missense NM_001407636.1:c.3911A>T NP_001394565.1:p.Asp1304Val missense NM_001407637.1:c.3911A>T NP_001394566.1:p.Asp1304Val missense NM_001407638.1:c.3911A>T NP_001394567.1:p.Asp1304Val missense NM_001407639.1:c.3914A>T NP_001394568.1:p.Asp1305Val missense NM_001407640.1:c.3914A>T NP_001394569.1:p.Asp1305Val missense NM_001407641.1:c.3914A>T NP_001394570.1:p.Asp1305Val missense NM_001407642.1:c.3914A>T NP_001394571.1:p.Asp1305Val missense NM_001407644.1:c.3911A>T NP_001394573.1:p.Asp1304Val missense NM_001407645.1:c.3911A>T NP_001394574.1:p.Asp1304Val missense NM_001407646.1:c.3905A>T NP_001394575.1:p.Asp1302Val missense NM_001407647.1:c.3905A>T NP_001394576.1:p.Asp1302Val missense NM_001407648.1:c.3791A>T NP_001394577.1:p.Asp1264Val missense NM_001407649.1:c.3788A>T NP_001394578.1:p.Asp1263Val missense NM_001407652.1:c.3914A>T NP_001394581.1:p.Asp1305Val missense NM_001407653.1:c.3836A>T NP_001394582.1:p.Asp1279Val missense NM_001407654.1:c.3836A>T NP_001394583.1:p.Asp1279Val missense NM_001407655.1:c.3836A>T NP_001394584.1:p.Asp1279Val missense NM_001407656.1:c.3836A>T NP_001394585.1:p.Asp1279Val missense NM_001407657.1:c.3836A>T NP_001394586.1:p.Asp1279Val missense NM_001407658.1:c.3836A>T NP_001394587.1:p.Asp1279Val missense NM_001407659.1:c.3833A>T NP_001394588.1:p.Asp1278Val missense NM_001407660.1:c.3833A>T NP_001394589.1:p.Asp1278Val missense NM_001407661.1:c.3833A>T NP_001394590.1:p.Asp1278Val missense NM_001407662.1:c.3833A>T NP_001394591.1:p.Asp1278Val missense NM_001407663.1:c.3836A>T NP_001394592.1:p.Asp1279Val missense NM_001407664.1:c.3791A>T NP_001394593.1:p.Asp1264Val missense NM_001407665.1:c.3791A>T NP_001394594.1:p.Asp1264Val missense NM_001407666.1:c.3791A>T NP_001394595.1:p.Asp1264Val missense NM_001407667.1:c.3791A>T NP_001394596.1:p.Asp1264Val missense NM_001407668.1:c.3791A>T NP_001394597.1:p.Asp1264Val missense NM_001407669.1:c.3791A>T NP_001394598.1:p.Asp1264Val missense NM_001407670.1:c.3788A>T NP_001394599.1:p.Asp1263Val missense NM_001407671.1:c.3788A>T NP_001394600.1:p.Asp1263Val missense NM_001407672.1:c.3788A>T NP_001394601.1:p.Asp1263Val missense NM_001407673.1:c.3788A>T NP_001394602.1:p.Asp1263Val missense NM_001407674.1:c.3791A>T NP_001394603.1:p.Asp1264Val missense NM_001407675.1:c.3791A>T NP_001394604.1:p.Asp1264Val missense NM_001407676.1:c.3791A>T NP_001394605.1:p.Asp1264Val missense NM_001407677.1:c.3791A>T NP_001394606.1:p.Asp1264Val missense NM_001407678.1:c.3791A>T NP_001394607.1:p.Asp1264Val missense NM_001407679.1:c.3791A>T NP_001394608.1:p.Asp1264Val missense NM_001407680.1:c.3791A>T NP_001394609.1:p.Asp1264Val missense NM_001407681.1:c.3791A>T NP_001394610.1:p.Asp1264Val missense NM_001407682.1:c.3791A>T NP_001394611.1:p.Asp1264Val missense NM_001407683.1:c.3791A>T NP_001394612.1:p.Asp1264Val missense NM_001407684.1:c.3914A>T NP_001394613.1:p.Asp1305Val missense NM_001407685.1:c.3788A>T NP_001394614.1:p.Asp1263Val missense NM_001407686.1:c.3788A>T NP_001394615.1:p.Asp1263Val missense NM_001407687.1:c.3788A>T NP_001394616.1:p.Asp1263Val missense NM_001407688.1:c.3788A>T NP_001394617.1:p.Asp1263Val missense NM_001407689.1:c.3788A>T NP_001394618.1:p.Asp1263Val missense NM_001407690.1:c.3788A>T NP_001394619.1:p.Asp1263Val missense NM_001407691.1:c.3788A>T NP_001394620.1:p.Asp1263Val missense NM_001407692.1:c.3773A>T NP_001394621.1:p.Asp1258Val missense NM_001407694.1:c.3773A>T NP_001394623.1:p.Asp1258Val missense NM_001407695.1:c.3773A>T NP_001394624.1:p.Asp1258Val missense NM_001407696.1:c.3773A>T NP_001394625.1:p.Asp1258Val missense NM_001407697.1:c.3773A>T NP_001394626.1:p.Asp1258Val missense NM_001407698.1:c.3773A>T NP_001394627.1:p.Asp1258Val missense NM_001407724.1:c.3773A>T NP_001394653.1:p.Asp1258Val missense NM_001407725.1:c.3773A>T NP_001394654.1:p.Asp1258Val missense NM_001407726.1:c.3773A>T NP_001394655.1:p.Asp1258Val missense NM_001407727.1:c.3773A>T NP_001394656.1:p.Asp1258Val missense NM_001407728.1:c.3773A>T NP_001394657.1:p.Asp1258Val missense NM_001407729.1:c.3773A>T NP_001394658.1:p.Asp1258Val missense NM_001407730.1:c.3773A>T NP_001394659.1:p.Asp1258Val missense NM_001407731.1:c.3773A>T NP_001394660.1:p.Asp1258Val missense NM_001407732.1:c.3773A>T NP_001394661.1:p.Asp1258Val missense NM_001407733.1:c.3773A>T NP_001394662.1:p.Asp1258Val missense NM_001407734.1:c.3773A>T NP_001394663.1:p.Asp1258Val missense NM_001407735.1:c.3773A>T NP_001394664.1:p.Asp1258Val missense NM_001407736.1:c.3773A>T NP_001394665.1:p.Asp1258Val missense NM_001407737.1:c.3773A>T NP_001394666.1:p.Asp1258Val missense NM_001407738.1:c.3773A>T NP_001394667.1:p.Asp1258Val missense NM_001407739.1:c.3773A>T NP_001394668.1:p.Asp1258Val missense NM_001407740.1:c.3770A>T NP_001394669.1:p.Asp1257Val missense NM_001407741.1:c.3770A>T NP_001394670.1:p.Asp1257Val missense NM_001407742.1:c.3770A>T NP_001394671.1:p.Asp1257Val missense NM_001407743.1:c.3770A>T NP_001394672.1:p.Asp1257Val missense NM_001407744.1:c.3770A>T NP_001394673.1:p.Asp1257Val missense NM_001407745.1:c.3770A>T NP_001394674.1:p.Asp1257Val missense NM_001407746.1:c.3770A>T NP_001394675.1:p.Asp1257Val missense NM_001407747.1:c.3770A>T NP_001394676.1:p.Asp1257Val missense NM_001407748.1:c.3770A>T NP_001394677.1:p.Asp1257Val missense NM_001407749.1:c.3770A>T NP_001394678.1:p.Asp1257Val missense NM_001407750.1:c.3773A>T NP_001394679.1:p.Asp1258Val missense NM_001407751.1:c.3773A>T NP_001394680.1:p.Asp1258Val missense NM_001407752.1:c.3773A>T NP_001394681.1:p.Asp1258Val missense NM_001407838.1:c.3770A>T NP_001394767.1:p.Asp1257Val missense NM_001407839.1:c.3770A>T NP_001394768.1:p.Asp1257Val missense NM_001407841.1:c.3770A>T NP_001394770.1:p.Asp1257Val missense NM_001407842.1:c.3770A>T NP_001394771.1:p.Asp1257Val missense NM_001407843.1:c.3770A>T NP_001394772.1:p.Asp1257Val missense NM_001407844.1:c.3770A>T NP_001394773.1:p.Asp1257Val missense NM_001407845.1:c.3770A>T NP_001394774.1:p.Asp1257Val missense NM_001407846.1:c.3770A>T NP_001394775.1:p.Asp1257Val missense NM_001407847.1:c.3770A>T NP_001394776.1:p.Asp1257Val missense NM_001407848.1:c.3770A>T NP_001394777.1:p.Asp1257Val missense NM_001407849.1:c.3770A>T NP_001394778.1:p.Asp1257Val missense NM_001407850.1:c.3773A>T NP_001394779.1:p.Asp1258Val missense NM_001407851.1:c.3773A>T NP_001394780.1:p.Asp1258Val missense NM_001407852.1:c.3773A>T NP_001394781.1:p.Asp1258Val missense NM_001407853.1:c.3701A>T NP_001394782.1:p.Asp1234Val missense NM_001407854.1:c.3914A>T NP_001394783.1:p.Asp1305Val missense NM_001407858.1:c.3914A>T NP_001394787.1:p.Asp1305Val missense NM_001407859.1:c.3914A>T NP_001394788.1:p.Asp1305Val missense NM_001407860.1:c.3911A>T NP_001394789.1:p.Asp1304Val missense NM_001407861.1:c.3911A>T NP_001394790.1:p.Asp1304Val missense NM_001407862.1:c.3713A>T NP_001394791.1:p.Asp1238Val missense NM_001407863.1:c.3791A>T NP_001394792.1:p.Asp1264Val missense NM_001407874.1:c.3710A>T NP_001394803.1:p.Asp1237Val missense NM_001407875.1:c.3710A>T NP_001394804.1:p.Asp1237Val missense NM_001407879.1:c.3704A>T NP_001394808.1:p.Asp1235Val missense NM_001407881.1:c.3704A>T NP_001394810.1:p.Asp1235Val missense NM_001407882.1:c.3704A>T NP_001394811.1:p.Asp1235Val missense NM_001407884.1:c.3704A>T NP_001394813.1:p.Asp1235Val missense NM_001407885.1:c.3704A>T NP_001394814.1:p.Asp1235Val missense NM_001407886.1:c.3704A>T NP_001394815.1:p.Asp1235Val missense NM_001407887.1:c.3704A>T NP_001394816.1:p.Asp1235Val missense NM_001407889.1:c.3704A>T NP_001394818.1:p.Asp1235Val missense NM_001407894.1:c.3701A>T NP_001394823.1:p.Asp1234Val missense NM_001407895.1:c.3701A>T NP_001394824.1:p.Asp1234Val missense NM_001407896.1:c.3701A>T NP_001394825.1:p.Asp1234Val missense NM_001407897.1:c.3701A>T NP_001394826.1:p.Asp1234Val missense NM_001407898.1:c.3701A>T NP_001394827.1:p.Asp1234Val missense NM_001407899.1:c.3701A>T NP_001394828.1:p.Asp1234Val missense NM_001407900.1:c.3704A>T NP_001394829.1:p.Asp1235Val missense NM_001407902.1:c.3704A>T NP_001394831.1:p.Asp1235Val missense NM_001407904.1:c.3704A>T NP_001394833.1:p.Asp1235Val missense NM_001407906.1:c.3704A>T NP_001394835.1:p.Asp1235Val missense NM_001407907.1:c.3704A>T NP_001394836.1:p.Asp1235Val missense NM_001407908.1:c.3704A>T NP_001394837.1:p.Asp1235Val missense NM_001407909.1:c.3704A>T NP_001394838.1:p.Asp1235Val missense NM_001407910.1:c.3704A>T NP_001394839.1:p.Asp1235Val missense NM_001407915.1:c.3701A>T NP_001394844.1:p.Asp1234Val missense NM_001407916.1:c.3701A>T NP_001394845.1:p.Asp1234Val missense NM_001407917.1:c.3701A>T NP_001394846.1:p.Asp1234Val missense NM_001407918.1:c.3701A>T NP_001394847.1:p.Asp1234Val missense NM_001407919.1:c.3791A>T NP_001394848.1:p.Asp1264Val missense NM_001407920.1:c.3650A>T NP_001394849.1:p.Asp1217Val missense NM_001407921.1:c.3650A>T NP_001394850.1:p.Asp1217Val missense NM_001407922.1:c.3650A>T NP_001394851.1:p.Asp1217Val missense NM_001407923.1:c.3650A>T NP_001394852.1:p.Asp1217Val missense NM_001407924.1:c.3650A>T NP_001394853.1:p.Asp1217Val missense NM_001407925.1:c.3650A>T NP_001394854.1:p.Asp1217Val missense NM_001407926.1:c.3650A>T NP_001394855.1:p.Asp1217Val missense NM_001407927.1:c.3650A>T NP_001394856.1:p.Asp1217Val missense NM_001407928.1:c.3650A>T NP_001394857.1:p.Asp1217Val missense NM_001407929.1:c.3650A>T NP_001394858.1:p.Asp1217Val missense NM_001407930.1:c.3647A>T NP_001394859.1:p.Asp1216Val missense NM_001407931.1:c.3647A>T NP_001394860.1:p.Asp1216Val missense NM_001407932.1:c.3647A>T NP_001394861.1:p.Asp1216Val missense NM_001407933.1:c.3650A>T NP_001394862.1:p.Asp1217Val missense NM_001407934.1:c.3647A>T NP_001394863.1:p.Asp1216Val missense NM_001407935.1:c.3650A>T NP_001394864.1:p.Asp1217Val missense NM_001407936.1:c.3647A>T NP_001394865.1:p.Asp1216Val missense NM_001407937.1:c.3791A>T NP_001394866.1:p.Asp1264Val missense NM_001407938.1:c.3791A>T NP_001394867.1:p.Asp1264Val missense NM_001407939.1:c.3791A>T NP_001394868.1:p.Asp1264Val missense NM_001407940.1:c.3788A>T NP_001394869.1:p.Asp1263Val missense NM_001407941.1:c.3788A>T NP_001394870.1:p.Asp1263Val missense NM_001407942.1:c.3773A>T NP_001394871.1:p.Asp1258Val missense NM_001407943.1:c.3770A>T NP_001394872.1:p.Asp1257Val missense NM_001407944.1:c.3773A>T NP_001394873.1:p.Asp1258Val missense NM_001407945.1:c.3773A>T NP_001394874.1:p.Asp1258Val missense NM_001407946.1:c.3581A>T NP_001394875.1:p.Asp1194Val missense NM_001407947.1:c.3581A>T NP_001394876.1:p.Asp1194Val missense NM_001407948.1:c.3581A>T NP_001394877.1:p.Asp1194Val missense NM_001407949.1:c.3581A>T NP_001394878.1:p.Asp1194Val missense NM_001407950.1:c.3581A>T NP_001394879.1:p.Asp1194Val missense NM_001407951.1:c.3581A>T NP_001394880.1:p.Asp1194Val missense NM_001407952.1:c.3581A>T NP_001394881.1:p.Asp1194Val missense NM_001407953.1:c.3581A>T NP_001394882.1:p.Asp1194Val missense NM_001407954.1:c.3578A>T NP_001394883.1:p.Asp1193Val missense NM_001407955.1:c.3578A>T NP_001394884.1:p.Asp1193Val missense NM_001407956.1:c.3578A>T NP_001394885.1:p.Asp1193Val missense NM_001407957.1:c.3581A>T NP_001394886.1:p.Asp1194Val missense NM_001407958.1:c.3578A>T NP_001394887.1:p.Asp1193Val missense NM_001407959.1:c.3533A>T NP_001394888.1:p.Asp1178Val missense NM_001407960.1:c.3533A>T NP_001394889.1:p.Asp1178Val missense NM_001407962.1:c.3530A>T NP_001394891.1:p.Asp1177Val missense NM_001407963.1:c.3533A>T NP_001394892.1:p.Asp1178Val missense NM_001407964.1:c.3770A>T NP_001394893.1:p.Asp1257Val missense NM_001407965.1:c.3410A>T NP_001394894.1:p.Asp1137Val missense NM_001407966.1:c.3026A>T NP_001394895.1:p.Asp1009Val missense NM_001407967.1:c.3026A>T NP_001394896.1:p.Asp1009Val missense NM_001407968.1:c.1310A>T NP_001394897.1:p.Asp437Val missense NM_001407969.1:c.1310A>T NP_001394898.1:p.Asp437Val missense NM_001407970.1:c.788-585A>T intron variant NM_001407971.1:c.788-585A>T intron variant NM_001407972.1:c.785-585A>T intron variant NM_001407973.1:c.788-585A>T intron variant NM_001407974.1:c.788-585A>T intron variant NM_001407975.1:c.788-585A>T intron variant NM_001407976.1:c.788-585A>T intron variant NM_001407977.1:c.788-585A>T intron variant NM_001407978.1:c.788-585A>T intron variant NM_001407979.1:c.788-585A>T intron variant NM_001407980.1:c.788-585A>T intron variant NM_001407981.1:c.788-585A>T intron variant NM_001407982.1:c.788-585A>T intron variant NM_001407983.1:c.788-585A>T intron variant NM_001407984.1:c.785-585A>T intron variant NM_001407985.1:c.785-585A>T intron variant NM_001407986.1:c.785-585A>T intron variant NM_001407990.1:c.788-585A>T intron variant NM_001407991.1:c.785-585A>T intron variant NM_001407992.1:c.785-585A>T intron variant NM_001407993.1:c.788-585A>T intron variant NM_001408392.1:c.785-585A>T intron variant NM_001408396.1:c.785-585A>T intron variant NM_001408397.1:c.785-585A>T intron variant NM_001408398.1:c.785-585A>T intron variant NM_001408399.1:c.785-585A>T intron variant NM_001408400.1:c.785-585A>T intron variant NM_001408401.1:c.785-585A>T intron variant NM_001408402.1:c.785-585A>T intron variant NM_001408403.1:c.788-585A>T intron variant NM_001408404.1:c.788-585A>T intron variant NM_001408406.1:c.791-594A>T intron variant NM_001408407.1:c.785-585A>T intron variant NM_001408408.1:c.779-585A>T intron variant NM_001408409.1:c.710-585A>T intron variant NM_001408410.1:c.647-585A>T intron variant NM_001408411.1:c.710-585A>T intron variant NM_001408412.1:c.710-585A>T intron variant NM_001408413.1:c.707-585A>T intron variant NM_001408414.1:c.710-585A>T intron variant NM_001408415.1:c.710-585A>T intron variant NM_001408416.1:c.707-585A>T intron variant NM_001408418.1:c.671-585A>T intron variant NM_001408419.1:c.671-585A>T intron variant NM_001408420.1:c.671-585A>T intron variant NM_001408421.1:c.668-585A>T intron variant NM_001408422.1:c.671-585A>T intron variant NM_001408423.1:c.671-585A>T intron variant NM_001408424.1:c.668-585A>T intron variant NM_001408425.1:c.665-585A>T intron variant NM_001408426.1:c.665-585A>T intron variant NM_001408427.1:c.665-585A>T intron variant NM_001408428.1:c.665-585A>T intron variant NM_001408429.1:c.665-585A>T intron variant NM_001408430.1:c.665-585A>T intron variant NM_001408431.1:c.668-585A>T intron variant NM_001408432.1:c.662-585A>T intron variant NM_001408433.1:c.662-585A>T intron variant NM_001408434.1:c.662-585A>T intron variant NM_001408435.1:c.662-585A>T intron variant NM_001408436.1:c.665-585A>T intron variant NM_001408437.1:c.665-585A>T intron variant NM_001408438.1:c.665-585A>T intron variant NM_001408439.1:c.665-585A>T intron variant NM_001408440.1:c.665-585A>T intron variant NM_001408441.1:c.665-585A>T intron variant NM_001408442.1:c.665-585A>T intron variant NM_001408443.1:c.665-585A>T intron variant NM_001408444.1:c.665-585A>T intron variant NM_001408445.1:c.662-585A>T intron variant NM_001408446.1:c.662-585A>T intron variant NM_001408447.1:c.662-585A>T intron variant NM_001408448.1:c.662-585A>T intron variant NM_001408450.1:c.662-585A>T intron variant NM_001408451.1:c.653-585A>T intron variant NM_001408452.1:c.647-585A>T intron variant NM_001408453.1:c.647-585A>T intron variant NM_001408454.1:c.647-585A>T intron variant NM_001408455.1:c.647-585A>T intron variant NM_001408456.1:c.647-585A>T intron variant NM_001408457.1:c.647-585A>T intron variant NM_001408458.1:c.647-585A>T intron variant NM_001408459.1:c.647-585A>T intron variant NM_001408460.1:c.647-585A>T intron variant NM_001408461.1:c.647-585A>T intron variant NM_001408462.1:c.644-585A>T intron variant NM_001408463.1:c.644-585A>T intron variant NM_001408464.1:c.644-585A>T intron variant NM_001408465.1:c.644-585A>T intron variant NM_001408466.1:c.647-585A>T intron variant NM_001408467.1:c.647-585A>T intron variant NM_001408468.1:c.644-585A>T intron variant NM_001408469.1:c.647-585A>T intron variant NM_001408470.1:c.644-585A>T intron variant NM_001408472.1:c.788-585A>T intron variant NM_001408473.1:c.785-585A>T intron variant NM_001408474.1:c.587-585A>T intron variant NM_001408475.1:c.584-585A>T intron variant NM_001408476.1:c.587-585A>T intron variant NM_001408478.1:c.578-585A>T intron variant NM_001408479.1:c.578-585A>T intron variant NM_001408480.1:c.578-585A>T intron variant NM_001408481.1:c.578-585A>T intron variant NM_001408482.1:c.578-585A>T intron variant NM_001408483.1:c.578-585A>T intron variant NM_001408484.1:c.578-585A>T intron variant NM_001408485.1:c.578-585A>T intron variant NM_001408489.1:c.578-585A>T intron variant NM_001408490.1:c.575-585A>T intron variant NM_001408491.1:c.575-585A>T intron variant NM_001408492.1:c.578-585A>T intron variant NM_001408493.1:c.575-585A>T intron variant NM_001408494.1:c.548-585A>T intron variant NM_001408495.1:c.545-585A>T intron variant NM_001408496.1:c.524-585A>T intron variant NM_001408497.1:c.524-585A>T intron variant NM_001408498.1:c.524-585A>T intron variant NM_001408499.1:c.524-585A>T intron variant NM_001408500.1:c.524-585A>T intron variant NM_001408501.1:c.524-585A>T intron variant NM_001408502.1:c.455-585A>T intron variant NM_001408503.1:c.521-585A>T intron variant NM_001408504.1:c.521-585A>T intron variant NM_001408505.1:c.521-585A>T intron variant NM_001408506.1:c.461-585A>T intron variant NM_001408507.1:c.461-585A>T intron variant NM_001408508.1:c.452-585A>T intron variant NM_001408509.1:c.452-585A>T intron variant NM_001408510.1:c.407-585A>T intron variant NM_001408511.1:c.404-585A>T intron variant NM_001408512.1:c.284-585A>T intron variant NM_001408513.1:c.578-585A>T intron variant NM_001408514.1:c.578-585A>T intron variant NM_007297.4:c.3773A>T NP_009228.2:p.Asp1258Val missense NM_007298.4:c.788-585A>T intron variant NM_007299.4:c.788-585A>T intron variant NM_007300.4:c.3914A>T NP_009231.2:p.Asp1305Val missense NR_027676.1:n.4050A>T NC_000017.11:g.43091617T>A NC_000017.10:g.41243634T>A NG_005905.2:g.126367A>T NG_087068.1:g.599T>A LRG_292:g.126367A>T LRG_292t1:c.3914A>T LRG_292p1:p.Asp1305Val - Protein change
- D1305V, D1258V, D1217V, D1238V, D1278V, D1279V, D1177V, D1193V, D1194V, D1216V, D1264V, D1009V, D1137V, D1178V, D1234V, D1235V, D1257V, D1304V, D1237V, D1263V, D1302V, D437V
- Other names
- -
- Canonical SPDI
- NC_000017.11:43091616:T:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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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. |
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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
12943 | 14735 | |
LOC126862571 | - | - | - | GRCh38 | - | 1640 |
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. |
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Uncertain significance (2) |
criteria provided, single submitter
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Nov 2, 2023 | RCV000083041.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 19, 2023 | RCV000549261.5 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Oct 11, 2023 | RCV000775151.15 | |
Likely benign (1) |
criteria provided, single submitter
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Oct 21, 2022 | RCV002307392.1 |
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. |
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Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003847832.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
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Likely benign
(Oct 21, 2022)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002600637.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Comment:
Variant summary: BRCA1 c.3914A>T (p.Asp1305Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Variant summary: BRCA1 c.3914A>T (p.Asp1305Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251160 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3914A>T has been reported in the literature in individuals with suspected predisposition to Hereditary Breast And Ovarian Cancer Syndrome (Machackova_2019) . This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At least one publication reports experimental evidence evaluating an impact on protein function (Bouwman_2020). These results showed no damaging effect of this variant on ability to complement BRCA1-deficient mouse embryonic stem cells in homologous recombination DNA repair (HRR) using cisplatin and olaparib sensitivity assays and a direct GFP HRR assay. HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Uncertain significance
(Oct 11, 2023)
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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: SCV000909285.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces aspartic acid with valine at codon 1305 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces aspartic acid with valine at codon 1305 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has reported that this variant does not impact BRCA1 function in a homology-mediated DNA repair and sensitivity to cisplatin and PARP inhibitor assays (PMID: 32546644). This variant has been detected in a suspected hereditary breast and ovarian cancer family (PMID: 31409081) and it also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_002612). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jan 19, 2023)
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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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Invitae
Accession: SCV000635930.5
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) … (more)
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 96920). This missense change has been observed in individual(s) with breast cancer (PMID: 21520333, 31409081). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1305 of the BRCA1 protein (p.Asp1305Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain Significance
(Nov 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004817726.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces aspartic acid with valine at codon 1305 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces aspartic acid with valine at codon 1305 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has reported that this variant does not impact BRCA1 function in a homology-mediated DNA repair and sensitivity to cisplatin and PARP inhibitor assays (PMID: 32546644). This variant has been detected in a suspected hereditary breast and ovarian cancer family (PMID: 31409081) and it also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_002612). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Jun 14, 2023)
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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: SCV001183042.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.D1305V variant (also known as c.3914A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide … (more)
The p.D1305V variant (also known as c.3914A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3914. The aspartic acid at codon 1305 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Jan 24, 2008)
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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: SCV000115115.3
First in ClinVar: Feb 09, 2014 Last updated: Sep 27, 2014 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Functional Categorization of BRCA1 Variants of Uncertain Clinical Significance in Homologous Recombination Repair Complementation Assays. | Bouwman P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2020 | PMID: 32546644 |
Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Twenty Years of BRCA1 and BRCA2 Molecular Analysis at MMCI - Current Developments for the Classification of Variants. | Machackova E | Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti | 2019 | PMID: 31409081 |
LOVD v.2.0: the next generation in gene variant databases. | Fokkema IF | Human mutation | 2011 | PMID: 21520333 |
Text-mined citations for rs431825402 ...
HelpRecord last updated Jul 15, 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.