ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3800T>C (p.Leu1267Ser)
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(8); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.3800T>C (p.Leu1267Ser)
Variation ID: 142031 Accession: VCV000142031.46
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091731 (GRCh38) [ NCBI UCSC ] 17: 41243748 (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 17, 2017 Oct 8, 2024 Dec 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.3800T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu1267Ser missense NM_001407571.1:c.3587T>C NP_001394500.1:p.Leu1196Ser missense NM_001407581.1:c.3800T>C NP_001394510.1:p.Leu1267Ser missense NM_001407582.1:c.3800T>C NP_001394511.1:p.Leu1267Ser missense NM_001407583.1:c.3800T>C NP_001394512.1:p.Leu1267Ser missense NM_001407585.1:c.3800T>C NP_001394514.1:p.Leu1267Ser missense NM_001407587.1:c.3797T>C NP_001394516.1:p.Leu1266Ser missense NM_001407590.1:c.3797T>C NP_001394519.1:p.Leu1266Ser missense NM_001407591.1:c.3797T>C NP_001394520.1:p.Leu1266Ser missense NM_001407593.1:c.3800T>C NP_001394522.1:p.Leu1267Ser missense NM_001407594.1:c.3800T>C NP_001394523.1:p.Leu1267Ser missense NM_001407596.1:c.3800T>C NP_001394525.1:p.Leu1267Ser missense NM_001407597.1:c.3800T>C NP_001394526.1:p.Leu1267Ser missense NM_001407598.1:c.3800T>C NP_001394527.1:p.Leu1267Ser missense NM_001407602.1:c.3800T>C NP_001394531.1:p.Leu1267Ser missense NM_001407603.1:c.3800T>C NP_001394532.1:p.Leu1267Ser missense NM_001407605.1:c.3800T>C NP_001394534.1:p.Leu1267Ser missense NM_001407610.1:c.3797T>C NP_001394539.1:p.Leu1266Ser missense NM_001407611.1:c.3797T>C NP_001394540.1:p.Leu1266Ser missense NM_001407612.1:c.3797T>C NP_001394541.1:p.Leu1266Ser missense NM_001407613.1:c.3797T>C NP_001394542.1:p.Leu1266Ser missense NM_001407614.1:c.3797T>C NP_001394543.1:p.Leu1266Ser missense NM_001407615.1:c.3797T>C NP_001394544.1:p.Leu1266Ser missense NM_001407616.1:c.3800T>C NP_001394545.1:p.Leu1267Ser missense NM_001407617.1:c.3800T>C NP_001394546.1:p.Leu1267Ser missense NM_001407618.1:c.3800T>C NP_001394547.1:p.Leu1267Ser missense NM_001407619.1:c.3800T>C NP_001394548.1:p.Leu1267Ser missense NM_001407620.1:c.3800T>C NP_001394549.1:p.Leu1267Ser missense NM_001407621.1:c.3800T>C NP_001394550.1:p.Leu1267Ser missense NM_001407622.1:c.3800T>C NP_001394551.1:p.Leu1267Ser missense NM_001407623.1:c.3800T>C NP_001394552.1:p.Leu1267Ser missense NM_001407624.1:c.3800T>C NP_001394553.1:p.Leu1267Ser missense NM_001407625.1:c.3800T>C NP_001394554.1:p.Leu1267Ser missense NM_001407626.1:c.3800T>C NP_001394555.1:p.Leu1267Ser missense NM_001407627.1:c.3797T>C NP_001394556.1:p.Leu1266Ser missense NM_001407628.1:c.3797T>C NP_001394557.1:p.Leu1266Ser missense NM_001407629.1:c.3797T>C NP_001394558.1:p.Leu1266Ser missense NM_001407630.1:c.3797T>C NP_001394559.1:p.Leu1266Ser missense NM_001407631.1:c.3797T>C NP_001394560.1:p.Leu1266Ser missense NM_001407632.1:c.3797T>C NP_001394561.1:p.Leu1266Ser missense NM_001407633.1:c.3797T>C NP_001394562.1:p.Leu1266Ser missense NM_001407634.1:c.3797T>C NP_001394563.1:p.Leu1266Ser missense NM_001407635.1:c.3797T>C NP_001394564.1:p.Leu1266Ser missense NM_001407636.1:c.3797T>C NP_001394565.1:p.Leu1266Ser missense NM_001407637.1:c.3797T>C NP_001394566.1:p.Leu1266Ser missense NM_001407638.1:c.3797T>C NP_001394567.1:p.Leu1266Ser missense NM_001407639.1:c.3800T>C NP_001394568.1:p.Leu1267Ser missense NM_001407640.1:c.3800T>C NP_001394569.1:p.Leu1267Ser missense NM_001407641.1:c.3800T>C NP_001394570.1:p.Leu1267Ser missense NM_001407642.1:c.3800T>C NP_001394571.1:p.Leu1267Ser missense NM_001407644.1:c.3797T>C NP_001394573.1:p.Leu1266Ser missense NM_001407645.1:c.3797T>C NP_001394574.1:p.Leu1266Ser missense NM_001407646.1:c.3791T>C NP_001394575.1:p.Leu1264Ser missense NM_001407647.1:c.3791T>C NP_001394576.1:p.Leu1264Ser missense NM_001407648.1:c.3677T>C NP_001394577.1:p.Leu1226Ser missense NM_001407649.1:c.3674T>C NP_001394578.1:p.Leu1225Ser missense NM_001407652.1:c.3800T>C NP_001394581.1:p.Leu1267Ser missense NM_001407653.1:c.3722T>C NP_001394582.1:p.Leu1241Ser missense NM_001407654.1:c.3722T>C NP_001394583.1:p.Leu1241Ser missense NM_001407655.1:c.3722T>C NP_001394584.1:p.Leu1241Ser missense NM_001407656.1:c.3722T>C NP_001394585.1:p.Leu1241Ser missense NM_001407657.1:c.3722T>C NP_001394586.1:p.Leu1241Ser missense NM_001407658.1:c.3722T>C NP_001394587.1:p.Leu1241Ser missense NM_001407659.1:c.3719T>C NP_001394588.1:p.Leu1240Ser missense NM_001407660.1:c.3719T>C NP_001394589.1:p.Leu1240Ser missense NM_001407661.1:c.3719T>C NP_001394590.1:p.Leu1240Ser missense NM_001407662.1:c.3719T>C NP_001394591.1:p.Leu1240Ser missense NM_001407663.1:c.3722T>C NP_001394592.1:p.Leu1241Ser missense NM_001407664.1:c.3677T>C NP_001394593.1:p.Leu1226Ser missense NM_001407665.1:c.3677T>C NP_001394594.1:p.Leu1226Ser missense NM_001407666.1:c.3677T>C NP_001394595.1:p.Leu1226Ser missense NM_001407667.1:c.3677T>C NP_001394596.1:p.Leu1226Ser missense NM_001407668.1:c.3677T>C NP_001394597.1:p.Leu1226Ser missense NM_001407669.1:c.3677T>C NP_001394598.1:p.Leu1226Ser missense NM_001407670.1:c.3674T>C NP_001394599.1:p.Leu1225Ser missense NM_001407671.1:c.3674T>C NP_001394600.1:p.Leu1225Ser missense NM_001407672.1:c.3674T>C NP_001394601.1:p.Leu1225Ser missense NM_001407673.1:c.3674T>C NP_001394602.1:p.Leu1225Ser missense NM_001407674.1:c.3677T>C NP_001394603.1:p.Leu1226Ser missense NM_001407675.1:c.3677T>C NP_001394604.1:p.Leu1226Ser missense NM_001407676.1:c.3677T>C NP_001394605.1:p.Leu1226Ser missense NM_001407677.1:c.3677T>C NP_001394606.1:p.Leu1226Ser missense NM_001407678.1:c.3677T>C NP_001394607.1:p.Leu1226Ser missense NM_001407679.1:c.3677T>C NP_001394608.1:p.Leu1226Ser missense NM_001407680.1:c.3677T>C NP_001394609.1:p.Leu1226Ser missense NM_001407681.1:c.3677T>C NP_001394610.1:p.Leu1226Ser missense NM_001407682.1:c.3677T>C NP_001394611.1:p.Leu1226Ser missense NM_001407683.1:c.3677T>C NP_001394612.1:p.Leu1226Ser missense NM_001407684.1:c.3800T>C NP_001394613.1:p.Leu1267Ser missense NM_001407685.1:c.3674T>C NP_001394614.1:p.Leu1225Ser missense NM_001407686.1:c.3674T>C NP_001394615.1:p.Leu1225Ser missense NM_001407687.1:c.3674T>C NP_001394616.1:p.Leu1225Ser missense NM_001407688.1:c.3674T>C NP_001394617.1:p.Leu1225Ser missense NM_001407689.1:c.3674T>C NP_001394618.1:p.Leu1225Ser missense NM_001407690.1:c.3674T>C NP_001394619.1:p.Leu1225Ser missense NM_001407691.1:c.3674T>C NP_001394620.1:p.Leu1225Ser missense NM_001407692.1:c.3659T>C NP_001394621.1:p.Leu1220Ser missense NM_001407694.1:c.3659T>C NP_001394623.1:p.Leu1220Ser missense NM_001407695.1:c.3659T>C NP_001394624.1:p.Leu1220Ser missense NM_001407696.1:c.3659T>C NP_001394625.1:p.Leu1220Ser missense NM_001407697.1:c.3659T>C NP_001394626.1:p.Leu1220Ser missense NM_001407698.1:c.3659T>C NP_001394627.1:p.Leu1220Ser missense NM_001407724.1:c.3659T>C NP_001394653.1:p.Leu1220Ser missense NM_001407725.1:c.3659T>C NP_001394654.1:p.Leu1220Ser missense NM_001407726.1:c.3659T>C NP_001394655.1:p.Leu1220Ser missense NM_001407727.1:c.3659T>C NP_001394656.1:p.Leu1220Ser missense NM_001407728.1:c.3659T>C NP_001394657.1:p.Leu1220Ser missense NM_001407729.1:c.3659T>C NP_001394658.1:p.Leu1220Ser missense NM_001407730.1:c.3659T>C NP_001394659.1:p.Leu1220Ser missense NM_001407731.1:c.3659T>C NP_001394660.1:p.Leu1220Ser missense NM_001407732.1:c.3659T>C NP_001394661.1:p.Leu1220Ser missense NM_001407733.1:c.3659T>C NP_001394662.1:p.Leu1220Ser missense NM_001407734.1:c.3659T>C NP_001394663.1:p.Leu1220Ser missense NM_001407735.1:c.3659T>C NP_001394664.1:p.Leu1220Ser missense NM_001407736.1:c.3659T>C NP_001394665.1:p.Leu1220Ser missense NM_001407737.1:c.3659T>C NP_001394666.1:p.Leu1220Ser missense NM_001407738.1:c.3659T>C NP_001394667.1:p.Leu1220Ser missense NM_001407739.1:c.3659T>C NP_001394668.1:p.Leu1220Ser missense NM_001407740.1:c.3656T>C NP_001394669.1:p.Leu1219Ser missense NM_001407741.1:c.3656T>C NP_001394670.1:p.Leu1219Ser missense NM_001407742.1:c.3656T>C NP_001394671.1:p.Leu1219Ser missense NM_001407743.1:c.3656T>C NP_001394672.1:p.Leu1219Ser missense NM_001407744.1:c.3656T>C NP_001394673.1:p.Leu1219Ser missense NM_001407745.1:c.3656T>C NP_001394674.1:p.Leu1219Ser missense NM_001407746.1:c.3656T>C NP_001394675.1:p.Leu1219Ser missense NM_001407747.1:c.3656T>C NP_001394676.1:p.Leu1219Ser missense NM_001407748.1:c.3656T>C NP_001394677.1:p.Leu1219Ser missense NM_001407749.1:c.3656T>C NP_001394678.1:p.Leu1219Ser missense NM_001407750.1:c.3659T>C NP_001394679.1:p.Leu1220Ser missense NM_001407751.1:c.3659T>C NP_001394680.1:p.Leu1220Ser missense NM_001407752.1:c.3659T>C NP_001394681.1:p.Leu1220Ser missense NM_001407838.1:c.3656T>C NP_001394767.1:p.Leu1219Ser missense NM_001407839.1:c.3656T>C NP_001394768.1:p.Leu1219Ser missense NM_001407841.1:c.3656T>C NP_001394770.1:p.Leu1219Ser missense NM_001407842.1:c.3656T>C NP_001394771.1:p.Leu1219Ser missense NM_001407843.1:c.3656T>C NP_001394772.1:p.Leu1219Ser missense NM_001407844.1:c.3656T>C NP_001394773.1:p.Leu1219Ser missense NM_001407845.1:c.3656T>C NP_001394774.1:p.Leu1219Ser missense NM_001407846.1:c.3656T>C NP_001394775.1:p.Leu1219Ser missense NM_001407847.1:c.3656T>C NP_001394776.1:p.Leu1219Ser missense NM_001407848.1:c.3656T>C NP_001394777.1:p.Leu1219Ser missense NM_001407849.1:c.3656T>C NP_001394778.1:p.Leu1219Ser missense NM_001407850.1:c.3659T>C NP_001394779.1:p.Leu1220Ser missense NM_001407851.1:c.3659T>C NP_001394780.1:p.Leu1220Ser missense NM_001407852.1:c.3659T>C NP_001394781.1:p.Leu1220Ser missense NM_001407853.1:c.3587T>C NP_001394782.1:p.Leu1196Ser missense NM_001407854.1:c.3800T>C NP_001394783.1:p.Leu1267Ser missense NM_001407858.1:c.3800T>C NP_001394787.1:p.Leu1267Ser missense NM_001407859.1:c.3800T>C NP_001394788.1:p.Leu1267Ser missense NM_001407860.1:c.3797T>C NP_001394789.1:p.Leu1266Ser missense NM_001407861.1:c.3797T>C NP_001394790.1:p.Leu1266Ser missense NM_001407862.1:c.3599T>C NP_001394791.1:p.Leu1200Ser missense NM_001407863.1:c.3677T>C NP_001394792.1:p.Leu1226Ser missense NM_001407874.1:c.3596T>C NP_001394803.1:p.Leu1199Ser missense NM_001407875.1:c.3596T>C NP_001394804.1:p.Leu1199Ser missense NM_001407879.1:c.3590T>C NP_001394808.1:p.Leu1197Ser missense NM_001407881.1:c.3590T>C NP_001394810.1:p.Leu1197Ser missense NM_001407882.1:c.3590T>C NP_001394811.1:p.Leu1197Ser missense NM_001407884.1:c.3590T>C NP_001394813.1:p.Leu1197Ser missense NM_001407885.1:c.3590T>C NP_001394814.1:p.Leu1197Ser missense NM_001407886.1:c.3590T>C NP_001394815.1:p.Leu1197Ser missense NM_001407887.1:c.3590T>C NP_001394816.1:p.Leu1197Ser missense NM_001407889.1:c.3590T>C NP_001394818.1:p.Leu1197Ser missense NM_001407894.1:c.3587T>C NP_001394823.1:p.Leu1196Ser missense NM_001407895.1:c.3587T>C NP_001394824.1:p.Leu1196Ser missense NM_001407896.1:c.3587T>C NP_001394825.1:p.Leu1196Ser missense NM_001407897.1:c.3587T>C NP_001394826.1:p.Leu1196Ser missense NM_001407898.1:c.3587T>C NP_001394827.1:p.Leu1196Ser missense NM_001407899.1:c.3587T>C NP_001394828.1:p.Leu1196Ser missense NM_001407900.1:c.3590T>C NP_001394829.1:p.Leu1197Ser missense NM_001407902.1:c.3590T>C NP_001394831.1:p.Leu1197Ser missense NM_001407904.1:c.3590T>C NP_001394833.1:p.Leu1197Ser missense NM_001407906.1:c.3590T>C NP_001394835.1:p.Leu1197Ser missense NM_001407907.1:c.3590T>C NP_001394836.1:p.Leu1197Ser missense NM_001407908.1:c.3590T>C NP_001394837.1:p.Leu1197Ser missense NM_001407909.1:c.3590T>C NP_001394838.1:p.Leu1197Ser missense NM_001407910.1:c.3590T>C NP_001394839.1:p.Leu1197Ser missense NM_001407915.1:c.3587T>C NP_001394844.1:p.Leu1196Ser missense NM_001407916.1:c.3587T>C NP_001394845.1:p.Leu1196Ser missense NM_001407917.1:c.3587T>C NP_001394846.1:p.Leu1196Ser missense NM_001407918.1:c.3587T>C NP_001394847.1:p.Leu1196Ser missense NM_001407919.1:c.3677T>C NP_001394848.1:p.Leu1226Ser missense NM_001407920.1:c.3536T>C NP_001394849.1:p.Leu1179Ser missense NM_001407921.1:c.3536T>C NP_001394850.1:p.Leu1179Ser missense NM_001407922.1:c.3536T>C NP_001394851.1:p.Leu1179Ser missense NM_001407923.1:c.3536T>C NP_001394852.1:p.Leu1179Ser missense NM_001407924.1:c.3536T>C NP_001394853.1:p.Leu1179Ser missense NM_001407925.1:c.3536T>C NP_001394854.1:p.Leu1179Ser missense NM_001407926.1:c.3536T>C NP_001394855.1:p.Leu1179Ser missense NM_001407927.1:c.3536T>C NP_001394856.1:p.Leu1179Ser missense NM_001407928.1:c.3536T>C NP_001394857.1:p.Leu1179Ser missense NM_001407929.1:c.3536T>C NP_001394858.1:p.Leu1179Ser missense NM_001407930.1:c.3533T>C NP_001394859.1:p.Leu1178Ser missense NM_001407931.1:c.3533T>C NP_001394860.1:p.Leu1178Ser missense NM_001407932.1:c.3533T>C NP_001394861.1:p.Leu1178Ser missense NM_001407933.1:c.3536T>C NP_001394862.1:p.Leu1179Ser missense NM_001407934.1:c.3533T>C NP_001394863.1:p.Leu1178Ser missense NM_001407935.1:c.3536T>C NP_001394864.1:p.Leu1179Ser missense NM_001407936.1:c.3533T>C NP_001394865.1:p.Leu1178Ser missense NM_001407937.1:c.3677T>C NP_001394866.1:p.Leu1226Ser missense NM_001407938.1:c.3677T>C NP_001394867.1:p.Leu1226Ser missense NM_001407939.1:c.3677T>C NP_001394868.1:p.Leu1226Ser missense NM_001407940.1:c.3674T>C NP_001394869.1:p.Leu1225Ser missense NM_001407941.1:c.3674T>C NP_001394870.1:p.Leu1225Ser missense NM_001407942.1:c.3659T>C NP_001394871.1:p.Leu1220Ser missense NM_001407943.1:c.3656T>C NP_001394872.1:p.Leu1219Ser missense NM_001407944.1:c.3659T>C NP_001394873.1:p.Leu1220Ser missense NM_001407945.1:c.3659T>C NP_001394874.1:p.Leu1220Ser missense NM_001407946.1:c.3467T>C NP_001394875.1:p.Leu1156Ser missense NM_001407947.1:c.3467T>C NP_001394876.1:p.Leu1156Ser missense NM_001407948.1:c.3467T>C NP_001394877.1:p.Leu1156Ser missense NM_001407949.1:c.3467T>C NP_001394878.1:p.Leu1156Ser missense NM_001407950.1:c.3467T>C NP_001394879.1:p.Leu1156Ser missense NM_001407951.1:c.3467T>C NP_001394880.1:p.Leu1156Ser missense NM_001407952.1:c.3467T>C NP_001394881.1:p.Leu1156Ser missense NM_001407953.1:c.3467T>C NP_001394882.1:p.Leu1156Ser missense NM_001407954.1:c.3464T>C NP_001394883.1:p.Leu1155Ser missense NM_001407955.1:c.3464T>C NP_001394884.1:p.Leu1155Ser missense NM_001407956.1:c.3464T>C NP_001394885.1:p.Leu1155Ser missense NM_001407957.1:c.3467T>C NP_001394886.1:p.Leu1156Ser missense NM_001407958.1:c.3464T>C NP_001394887.1:p.Leu1155Ser missense NM_001407959.1:c.3419T>C NP_001394888.1:p.Leu1140Ser missense NM_001407960.1:c.3419T>C NP_001394889.1:p.Leu1140Ser missense NM_001407962.1:c.3416T>C NP_001394891.1:p.Leu1139Ser missense NM_001407963.1:c.3419T>C NP_001394892.1:p.Leu1140Ser missense NM_001407964.1:c.3656T>C NP_001394893.1:p.Leu1219Ser missense NM_001407965.1:c.3296T>C NP_001394894.1:p.Leu1099Ser missense NM_001407966.1:c.2912T>C NP_001394895.1:p.Leu971Ser missense NM_001407967.1:c.2912T>C NP_001394896.1:p.Leu971Ser missense NM_001407968.1:c.1196T>C NP_001394897.1:p.Leu399Ser missense NM_001407969.1:c.1196T>C NP_001394898.1:p.Leu399Ser missense NM_001407970.1:c.788-699T>C intron variant NM_001407971.1:c.788-699T>C intron variant NM_001407972.1:c.785-699T>C intron variant NM_001407973.1:c.788-699T>C intron variant NM_001407974.1:c.788-699T>C intron variant NM_001407975.1:c.788-699T>C intron variant NM_001407976.1:c.788-699T>C intron variant NM_001407977.1:c.788-699T>C intron variant NM_001407978.1:c.788-699T>C intron variant NM_001407979.1:c.788-699T>C intron variant NM_001407980.1:c.788-699T>C intron variant NM_001407981.1:c.788-699T>C intron variant NM_001407982.1:c.788-699T>C intron variant NM_001407983.1:c.788-699T>C intron variant NM_001407984.1:c.785-699T>C intron variant NM_001407985.1:c.785-699T>C intron variant NM_001407986.1:c.785-699T>C intron variant NM_001407990.1:c.788-699T>C intron variant NM_001407991.1:c.785-699T>C intron variant NM_001407992.1:c.785-699T>C intron variant NM_001407993.1:c.788-699T>C intron variant NM_001408392.1:c.785-699T>C intron variant NM_001408396.1:c.785-699T>C intron variant NM_001408397.1:c.785-699T>C intron variant NM_001408398.1:c.785-699T>C intron variant NM_001408399.1:c.785-699T>C intron variant NM_001408400.1:c.785-699T>C intron variant NM_001408401.1:c.785-699T>C intron variant NM_001408402.1:c.785-699T>C intron variant NM_001408403.1:c.788-699T>C intron variant NM_001408404.1:c.788-699T>C intron variant NM_001408406.1:c.791-708T>C intron variant NM_001408407.1:c.785-699T>C intron variant NM_001408408.1:c.779-699T>C intron variant NM_001408409.1:c.710-699T>C intron variant NM_001408410.1:c.647-699T>C intron variant NM_001408411.1:c.710-699T>C intron variant NM_001408412.1:c.710-699T>C intron variant NM_001408413.1:c.707-699T>C intron variant NM_001408414.1:c.710-699T>C intron variant NM_001408415.1:c.710-699T>C intron variant NM_001408416.1:c.707-699T>C intron variant NM_001408418.1:c.671-699T>C intron variant NM_001408419.1:c.671-699T>C intron variant NM_001408420.1:c.671-699T>C intron variant NM_001408421.1:c.668-699T>C intron variant NM_001408422.1:c.671-699T>C intron variant NM_001408423.1:c.671-699T>C intron variant NM_001408424.1:c.668-699T>C intron variant NM_001408425.1:c.665-699T>C intron variant NM_001408426.1:c.665-699T>C intron variant NM_001408427.1:c.665-699T>C intron variant NM_001408428.1:c.665-699T>C intron variant NM_001408429.1:c.665-699T>C intron variant NM_001408430.1:c.665-699T>C intron variant NM_001408431.1:c.668-699T>C intron variant NM_001408432.1:c.662-699T>C intron variant NM_001408433.1:c.662-699T>C intron variant NM_001408434.1:c.662-699T>C intron variant NM_001408435.1:c.662-699T>C intron variant NM_001408436.1:c.665-699T>C intron variant NM_001408437.1:c.665-699T>C intron variant NM_001408438.1:c.665-699T>C intron variant NM_001408439.1:c.665-699T>C intron variant NM_001408440.1:c.665-699T>C intron variant NM_001408441.1:c.665-699T>C intron variant NM_001408442.1:c.665-699T>C intron variant NM_001408443.1:c.665-699T>C intron variant NM_001408444.1:c.665-699T>C intron variant NM_001408445.1:c.662-699T>C intron variant NM_001408446.1:c.662-699T>C intron variant NM_001408447.1:c.662-699T>C intron variant NM_001408448.1:c.662-699T>C intron variant NM_001408450.1:c.662-699T>C intron variant NM_001408451.1:c.653-699T>C intron variant NM_001408452.1:c.647-699T>C intron variant NM_001408453.1:c.647-699T>C intron variant NM_001408454.1:c.647-699T>C intron variant NM_001408455.1:c.647-699T>C intron variant NM_001408456.1:c.647-699T>C intron variant NM_001408457.1:c.647-699T>C intron variant NM_001408458.1:c.647-699T>C intron variant NM_001408459.1:c.647-699T>C intron variant NM_001408460.1:c.647-699T>C intron variant NM_001408461.1:c.647-699T>C intron variant NM_001408462.1:c.644-699T>C intron variant NM_001408463.1:c.644-699T>C intron variant NM_001408464.1:c.644-699T>C intron variant NM_001408465.1:c.644-699T>C intron variant NM_001408466.1:c.647-699T>C intron variant NM_001408467.1:c.647-699T>C intron variant NM_001408468.1:c.644-699T>C intron variant NM_001408469.1:c.647-699T>C intron variant NM_001408470.1:c.644-699T>C intron variant NM_001408472.1:c.788-699T>C intron variant NM_001408473.1:c.785-699T>C intron variant NM_001408474.1:c.587-699T>C intron variant NM_001408475.1:c.584-699T>C intron variant NM_001408476.1:c.587-699T>C intron variant NM_001408478.1:c.578-699T>C intron variant NM_001408479.1:c.578-699T>C intron variant NM_001408480.1:c.578-699T>C intron variant NM_001408481.1:c.578-699T>C intron variant NM_001408482.1:c.578-699T>C intron variant NM_001408483.1:c.578-699T>C intron variant NM_001408484.1:c.578-699T>C intron variant NM_001408485.1:c.578-699T>C intron variant NM_001408489.1:c.578-699T>C intron variant NM_001408490.1:c.575-699T>C intron variant NM_001408491.1:c.575-699T>C intron variant NM_001408492.1:c.578-699T>C intron variant NM_001408493.1:c.575-699T>C intron variant NM_001408494.1:c.548-699T>C intron variant NM_001408495.1:c.545-699T>C intron variant NM_001408496.1:c.524-699T>C intron variant NM_001408497.1:c.524-699T>C intron variant NM_001408498.1:c.524-699T>C intron variant NM_001408499.1:c.524-699T>C intron variant NM_001408500.1:c.524-699T>C intron variant NM_001408501.1:c.524-699T>C intron variant NM_001408502.1:c.455-699T>C intron variant NM_001408503.1:c.521-699T>C intron variant NM_001408504.1:c.521-699T>C intron variant NM_001408505.1:c.521-699T>C intron variant NM_001408506.1:c.461-699T>C intron variant NM_001408507.1:c.461-699T>C intron variant NM_001408508.1:c.452-699T>C intron variant NM_001408509.1:c.452-699T>C intron variant NM_001408510.1:c.407-699T>C intron variant NM_001408511.1:c.404-699T>C intron variant NM_001408512.1:c.284-699T>C intron variant NM_001408513.1:c.578-699T>C intron variant NM_001408514.1:c.578-699T>C intron variant NM_007297.4:c.3659T>C NP_009228.2:p.Leu1220Ser missense NM_007298.4:c.788-699T>C intron variant NM_007299.4:c.788-699T>C intron variant NM_007300.4:c.3800T>C NP_009231.2:p.Leu1267Ser missense NR_027676.1:n.3936T>C NC_000017.11:g.43091731A>G NC_000017.10:g.41243748A>G NG_005905.2:g.126253T>C NG_087068.1:g.713A>G LRG_292:g.126253T>C LRG_292t1:c.3800T>C LRG_292p1:p.Leu1267Ser P38398:p.Leu1267Ser - Protein change
- L1267S, L1220S, L1178S, L1099S, L1140S, L1197S, L1200S, L1226S, L1240S, L1241S, L399S, L1139S, L1155S, L1156S, L1196S, L1225S, L971S, L1179S, L1199S, L1219S, L1264S, L1266S
- Other names
- p.L1267S:TTA>TCA
- Canonical SPDI
- NC_000017.11:43091730:A:G
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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 |
13037 | 14843 | |
LOC126862571 | - | - | - | GRCh38 | - | 1651 |
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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Aug 14, 2023 | RCV000130824.23 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 1, 2021 | RCV000589536.29 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Nov 17, 2023 | RCV000460978.22 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Dec 13, 2023 | RCV003998081.2 |
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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Uncertain significance
(Jan 04, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210156.12
First in ClinVar: Feb 24, 2015 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted BRCA1 c.3800T>C at the cDNA level, p.Leu1267Ser (L1267S) at the protein level, and results in the change of a Leucine to … (more)
This variant is denoted BRCA1 c.3800T>C at the cDNA level, p.Leu1267Ser (L1267S) at the protein level, and results in the change of a Leucine to a Serine (TTA>TCA). Functional studies by Bouwman et al. (2013) suggest that BRCA1 Leu1267Ser may be a neutral variant based on insensitivity to cisplatin and ability to support growth similar to controls in BRCA1-deficient mouse embryonic stem cells. BRCA1 Leu1267Ser was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Leu1267Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
|
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Uncertain significance
(Aug 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888900.2
First in ClinVar: Mar 17, 2018 Last updated: Jan 03, 2022 |
|
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Likely benign
(Nov 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000549344.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
|
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Uncertain Significance
(Dec 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004817744.1
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)
|
Comment:
This missense variant replaces leucine with serine at codon 1267 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces leucine with serine at codon 1267 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). Functional studies have reported that this variant does not impact on BRCA1 function in cisplatin and Olaparib sensitivity and homology-directed repair assays using mouse Brca1-deficient embryonic stem cells (PMID: 23867111, 32546644). This variant has been detected in a breast cancer case-control meta-analysis in 4/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001533). A multifactorial analysis has reported a likelihood ratio for pathogenicity based on tumor pathology of 0.21 (PMID: 31131967). 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: 2
|
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Uncertain significance
(Feb 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699074.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
|
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Uncertain significance
(Jun 10, 2021)
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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
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV001737436.2
First in ClinVar: Jun 19, 2021 Last updated: Jun 23, 2021 |
Comment:
The BRCA1 c.3800T>C (p.Leu1267Ser) missense change is absent in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/ ). Six of seven in silico tools predict a benign effect of … (more)
The BRCA1 c.3800T>C (p.Leu1267Ser) missense change is absent in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/ ). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4). Functional studies have shown that this change can rescue the proliferation defect of Brca1-deficient mouse embryonic stem cells similar to wild-type and also decrease sensitivity to cisplatin, suggesting that this change does not affect protein function (BS3_Supporting; PMID: 23867111). This variant is absent in the FLOSSIES database which contains genetic variants from women older than 70 years of age who have never had cancer (https://whi.color.com/). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting, BS3_Supporting, BP4. (less)
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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
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003846271.1
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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Uncertain significance
(Aug 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000688453.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces leucine with serine at codon 1267 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces leucine with serine at codon 1267 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). Functional studies have reported that this variant does not impact on BRCA1 function in cisplatin and Olaparib sensitivity and homology-directed repair assays using mouse Brca1-deficient embryonic stem cells (PMID: 23867111, 32546644). This variant has been detected in a breast cancer case-control meta-analysis in 4/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001533). A multifactorial analysis has reported a likelihood ratio for pathogenicity based on tumor pathology of 0.21 (PMID: 31131967). 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
(Sep 06, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185720.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.L1267S variant (also known as c.3800T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.L1267S variant (also known as c.3800T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3800. The leucine at codon 1267 is replaced by serine, an amino acid with dissimilar properties. In a cohort of 300 deceased patients, who underwent whole genome sequencing for 60 autosomal dominant cancer predisposition genes, this variant was detected and classified as likely benign by the authors. However, the specific phenotype of the patient(s) with this alteration was not reported (He KY et al. PLoS ONE, 2016 Dec;11:e0167847). This alteration has been reported as neutral in high-throughput complementation assays performed in mouse embryonic stem cells (Bouwman P. et al. Cancer Discov. 2013 Oct;3(10):1142-55; Bouwman P. et al. Clin Cancer Res. 2020 09;26(17):4559-4568). 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
(Apr 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001747805.19
First in ClinVar: Jul 10, 2021 Last updated: Oct 08, 2024 |
Number of individuals with the variant: 1
|
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 |
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records. | He KY | PloS one | 2016 | PMID: 27930734 |
A high-throughput functional complementation assay for classification of BRCA1 missense variants. | Bouwman P | Cancer discovery | 2013 | PMID: 23867111 |
Interlaboratory diagnostic validation of conformation-sensitive capillary electrophoresis for mutation scanning. | Mattocks CJ | Clinical chemistry | 2010 | PMID: 20167696 |
Text-mined citations for rs587782190 ...
HelpRecord last updated Oct 13, 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.