This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1531 of the BRCA1 protein (p.Val1531Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1715651). 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. 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.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4592T>C (p.Val1531Ala)
Germline
Classification
Help
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.
(1)
Help
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
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4592T>C (p.Val1531Ala)
Variation ID: 1715651 Accession: VCV001715651.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074414 (GRCh38) [ NCBI UCSC ] 17: 41226431 (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 Nov 5, 2022 Feb 20, 2024 Oct 13, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4592T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Val1531Ala missense NM_001407571.1:c.4379T>C NP_001394500.1:p.Val1460Ala missense NM_001407581.1:c.4658T>C NP_001394510.1:p.Val1553Ala missense NM_001407582.1:c.4658T>C NP_001394511.1:p.Val1553Ala missense NM_001407583.1:c.4655T>C NP_001394512.1:p.Val1552Ala missense NM_001407585.1:c.4655T>C NP_001394514.1:p.Val1552Ala missense NM_001407587.1:c.4655T>C NP_001394516.1:p.Val1552Ala missense NM_001407590.1:c.4652T>C NP_001394519.1:p.Val1551Ala missense NM_001407591.1:c.4652T>C NP_001394520.1:p.Val1551Ala missense NM_001407593.1:c.4592T>C NP_001394522.1:p.Val1531Ala missense NM_001407594.1:c.4592T>C NP_001394523.1:p.Val1531Ala missense NM_001407596.1:c.4592T>C NP_001394525.1:p.Val1531Ala missense NM_001407597.1:c.4592T>C NP_001394526.1:p.Val1531Ala missense NM_001407598.1:c.4592T>C NP_001394527.1:p.Val1531Ala missense NM_001407602.1:c.4592T>C NP_001394531.1:p.Val1531Ala missense NM_001407603.1:c.4592T>C NP_001394532.1:p.Val1531Ala missense NM_001407605.1:c.4592T>C NP_001394534.1:p.Val1531Ala missense NM_001407610.1:c.4589T>C NP_001394539.1:p.Val1530Ala missense NM_001407611.1:c.4589T>C NP_001394540.1:p.Val1530Ala missense NM_001407612.1:c.4589T>C NP_001394541.1:p.Val1530Ala missense NM_001407613.1:c.4589T>C NP_001394542.1:p.Val1530Ala missense NM_001407614.1:c.4589T>C NP_001394543.1:p.Val1530Ala missense NM_001407615.1:c.4589T>C NP_001394544.1:p.Val1530Ala missense NM_001407616.1:c.4589T>C NP_001394545.1:p.Val1530Ala missense NM_001407617.1:c.4589T>C NP_001394546.1:p.Val1530Ala missense NM_001407618.1:c.4589T>C NP_001394547.1:p.Val1530Ala missense NM_001407619.1:c.4589T>C NP_001394548.1:p.Val1530Ala missense NM_001407620.1:c.4589T>C NP_001394549.1:p.Val1530Ala missense NM_001407621.1:c.4589T>C NP_001394550.1:p.Val1530Ala missense NM_001407622.1:c.4589T>C NP_001394551.1:p.Val1530Ala missense NM_001407623.1:c.4589T>C NP_001394552.1:p.Val1530Ala missense NM_001407624.1:c.4589T>C NP_001394553.1:p.Val1530Ala missense NM_001407625.1:c.4589T>C NP_001394554.1:p.Val1530Ala missense NM_001407626.1:c.4589T>C NP_001394555.1:p.Val1530Ala missense NM_001407627.1:c.4586T>C NP_001394556.1:p.Val1529Ala missense NM_001407628.1:c.4586T>C NP_001394557.1:p.Val1529Ala missense NM_001407629.1:c.4586T>C NP_001394558.1:p.Val1529Ala missense NM_001407630.1:c.4586T>C NP_001394559.1:p.Val1529Ala missense NM_001407631.1:c.4586T>C NP_001394560.1:p.Val1529Ala missense NM_001407632.1:c.4586T>C NP_001394561.1:p.Val1529Ala missense NM_001407633.1:c.4586T>C NP_001394562.1:p.Val1529Ala missense NM_001407634.1:c.4586T>C NP_001394563.1:p.Val1529Ala missense NM_001407635.1:c.4586T>C NP_001394564.1:p.Val1529Ala missense NM_001407636.1:c.4586T>C NP_001394565.1:p.Val1529Ala missense NM_001407637.1:c.4586T>C NP_001394566.1:p.Val1529Ala missense NM_001407638.1:c.4586T>C NP_001394567.1:p.Val1529Ala missense NM_001407639.1:c.4586T>C NP_001394568.1:p.Val1529Ala missense NM_001407640.1:c.4586T>C NP_001394569.1:p.Val1529Ala missense NM_001407641.1:c.4586T>C NP_001394570.1:p.Val1529Ala missense NM_001407642.1:c.4586T>C NP_001394571.1:p.Val1529Ala missense NM_001407644.1:c.4583T>C NP_001394573.1:p.Val1528Ala missense NM_001407645.1:c.4583T>C NP_001394574.1:p.Val1528Ala missense NM_001407646.1:c.4580T>C NP_001394575.1:p.Val1527Ala missense NM_001407647.1:c.4577T>C NP_001394576.1:p.Val1526Ala missense NM_001407648.1:c.4535T>C NP_001394577.1:p.Val1512Ala missense NM_001407649.1:c.4532T>C NP_001394578.1:p.Val1511Ala missense NM_001407652.1:c.4592T>C NP_001394581.1:p.Val1531Ala missense NM_001407653.1:c.4514T>C NP_001394582.1:p.Val1505Ala missense NM_001407654.1:c.4514T>C NP_001394583.1:p.Val1505Ala missense NM_001407655.1:c.4514T>C NP_001394584.1:p.Val1505Ala missense NM_001407656.1:c.4511T>C NP_001394585.1:p.Val1504Ala missense NM_001407657.1:c.4511T>C NP_001394586.1:p.Val1504Ala missense NM_001407658.1:c.4511T>C NP_001394587.1:p.Val1504Ala missense NM_001407659.1:c.4508T>C NP_001394588.1:p.Val1503Ala missense NM_001407660.1:c.4508T>C NP_001394589.1:p.Val1503Ala missense NM_001407661.1:c.4508T>C NP_001394590.1:p.Val1503Ala missense NM_001407662.1:c.4508T>C NP_001394591.1:p.Val1503Ala missense NM_001407663.1:c.4508T>C NP_001394592.1:p.Val1503Ala missense NM_001407664.1:c.4469T>C NP_001394593.1:p.Val1490Ala missense NM_001407665.1:c.4469T>C NP_001394594.1:p.Val1490Ala missense NM_001407666.1:c.4469T>C NP_001394595.1:p.Val1490Ala missense NM_001407667.1:c.4469T>C NP_001394596.1:p.Val1490Ala missense NM_001407668.1:c.4469T>C NP_001394597.1:p.Val1490Ala missense NM_001407669.1:c.4469T>C NP_001394598.1:p.Val1490Ala missense NM_001407670.1:c.4466T>C NP_001394599.1:p.Val1489Ala missense NM_001407671.1:c.4466T>C NP_001394600.1:p.Val1489Ala missense NM_001407672.1:c.4466T>C NP_001394601.1:p.Val1489Ala missense NM_001407673.1:c.4466T>C NP_001394602.1:p.Val1489Ala missense NM_001407674.1:c.4466T>C NP_001394603.1:p.Val1489Ala missense NM_001407675.1:c.4466T>C NP_001394604.1:p.Val1489Ala missense NM_001407676.1:c.4466T>C NP_001394605.1:p.Val1489Ala missense NM_001407677.1:c.4466T>C NP_001394606.1:p.Val1489Ala missense NM_001407678.1:c.4466T>C NP_001394607.1:p.Val1489Ala missense NM_001407679.1:c.4466T>C NP_001394608.1:p.Val1489Ala missense NM_001407680.1:c.4466T>C NP_001394609.1:p.Val1489Ala missense NM_001407681.1:c.4463T>C NP_001394610.1:p.Val1488Ala missense NM_001407682.1:c.4463T>C NP_001394611.1:p.Val1488Ala missense NM_001407683.1:c.4463T>C NP_001394612.1:p.Val1488Ala missense NM_001407684.1:c.4592T>C NP_001394613.1:p.Val1531Ala missense NM_001407685.1:c.4463T>C NP_001394614.1:p.Val1488Ala missense NM_001407686.1:c.4463T>C NP_001394615.1:p.Val1488Ala missense NM_001407687.1:c.4463T>C NP_001394616.1:p.Val1488Ala missense NM_001407688.1:c.4463T>C NP_001394617.1:p.Val1488Ala missense NM_001407689.1:c.4463T>C NP_001394618.1:p.Val1488Ala missense NM_001407690.1:c.4460T>C NP_001394619.1:p.Val1487Ala missense NM_001407691.1:c.4460T>C NP_001394620.1:p.Val1487Ala missense NM_001407692.1:c.4451T>C NP_001394621.1:p.Val1484Ala missense NM_001407694.1:c.4451T>C NP_001394623.1:p.Val1484Ala missense NM_001407695.1:c.4451T>C NP_001394624.1:p.Val1484Ala missense NM_001407696.1:c.4451T>C NP_001394625.1:p.Val1484Ala missense NM_001407697.1:c.4451T>C NP_001394626.1:p.Val1484Ala missense NM_001407698.1:c.4451T>C NP_001394627.1:p.Val1484Ala missense NM_001407724.1:c.4451T>C NP_001394653.1:p.Val1484Ala missense NM_001407725.1:c.4451T>C NP_001394654.1:p.Val1484Ala missense NM_001407726.1:c.4451T>C NP_001394655.1:p.Val1484Ala missense NM_001407727.1:c.4451T>C NP_001394656.1:p.Val1484Ala missense NM_001407728.1:c.4451T>C NP_001394657.1:p.Val1484Ala missense NM_001407729.1:c.4451T>C NP_001394658.1:p.Val1484Ala missense NM_001407730.1:c.4451T>C NP_001394659.1:p.Val1484Ala missense NM_001407731.1:c.4451T>C NP_001394660.1:p.Val1484Ala missense NM_001407732.1:c.4448T>C NP_001394661.1:p.Val1483Ala missense NM_001407733.1:c.4448T>C NP_001394662.1:p.Val1483Ala missense NM_001407734.1:c.4448T>C NP_001394663.1:p.Val1483Ala missense NM_001407735.1:c.4448T>C NP_001394664.1:p.Val1483Ala missense NM_001407736.1:c.4448T>C NP_001394665.1:p.Val1483Ala missense NM_001407737.1:c.4448T>C NP_001394666.1:p.Val1483Ala missense NM_001407738.1:c.4448T>C NP_001394667.1:p.Val1483Ala missense NM_001407739.1:c.4448T>C NP_001394668.1:p.Val1483Ala missense NM_001407740.1:c.4448T>C NP_001394669.1:p.Val1483Ala missense NM_001407741.1:c.4448T>C NP_001394670.1:p.Val1483Ala missense NM_001407742.1:c.4448T>C NP_001394671.1:p.Val1483Ala missense NM_001407743.1:c.4448T>C NP_001394672.1:p.Val1483Ala missense NM_001407744.1:c.4448T>C NP_001394673.1:p.Val1483Ala missense NM_001407745.1:c.4448T>C NP_001394674.1:p.Val1483Ala missense NM_001407746.1:c.4448T>C NP_001394675.1:p.Val1483Ala missense NM_001407747.1:c.4448T>C NP_001394676.1:p.Val1483Ala missense NM_001407748.1:c.4448T>C NP_001394677.1:p.Val1483Ala missense NM_001407749.1:c.4448T>C NP_001394678.1:p.Val1483Ala missense NM_001407750.1:c.4448T>C NP_001394679.1:p.Val1483Ala missense NM_001407751.1:c.4448T>C NP_001394680.1:p.Val1483Ala missense NM_001407752.1:c.4448T>C NP_001394681.1:p.Val1483Ala missense NM_001407838.1:c.4445T>C NP_001394767.1:p.Val1482Ala missense NM_001407839.1:c.4445T>C NP_001394768.1:p.Val1482Ala missense NM_001407841.1:c.4445T>C NP_001394770.1:p.Val1482Ala missense NM_001407842.1:c.4445T>C NP_001394771.1:p.Val1482Ala missense NM_001407843.1:c.4445T>C NP_001394772.1:p.Val1482Ala missense NM_001407844.1:c.4445T>C NP_001394773.1:p.Val1482Ala missense NM_001407845.1:c.4445T>C NP_001394774.1:p.Val1482Ala missense NM_001407846.1:c.4445T>C NP_001394775.1:p.Val1482Ala missense NM_001407847.1:c.4445T>C NP_001394776.1:p.Val1482Ala missense NM_001407848.1:c.4445T>C NP_001394777.1:p.Val1482Ala missense NM_001407849.1:c.4445T>C NP_001394778.1:p.Val1482Ala missense NM_001407850.1:c.4445T>C NP_001394779.1:p.Val1482Ala missense NM_001407851.1:c.4445T>C NP_001394780.1:p.Val1482Ala missense NM_001407852.1:c.4445T>C NP_001394781.1:p.Val1482Ala missense NM_001407853.1:c.4445T>C NP_001394782.1:p.Val1482Ala missense NM_001407854.1:c.4592T>C NP_001394783.1:p.Val1531Ala missense NM_001407858.1:c.4589T>C NP_001394787.1:p.Val1530Ala missense NM_001407859.1:c.4589T>C NP_001394788.1:p.Val1530Ala missense NM_001407860.1:c.4589T>C NP_001394789.1:p.Val1530Ala missense NM_001407861.1:c.4586T>C NP_001394790.1:p.Val1529Ala missense NM_001407862.1:c.4391T>C NP_001394791.1:p.Val1464Ala missense NM_001407863.1:c.4466T>C NP_001394792.1:p.Val1489Ala missense NM_001407874.1:c.4385T>C NP_001394803.1:p.Val1462Ala missense NM_001407875.1:c.4385T>C NP_001394804.1:p.Val1462Ala missense NM_001407879.1:c.4382T>C NP_001394808.1:p.Val1461Ala missense NM_001407881.1:c.4382T>C NP_001394810.1:p.Val1461Ala missense NM_001407882.1:c.4382T>C NP_001394811.1:p.Val1461Ala missense NM_001407884.1:c.4382T>C NP_001394813.1:p.Val1461Ala missense NM_001407885.1:c.4382T>C NP_001394814.1:p.Val1461Ala missense NM_001407886.1:c.4382T>C NP_001394815.1:p.Val1461Ala missense NM_001407887.1:c.4382T>C NP_001394816.1:p.Val1461Ala missense NM_001407889.1:c.4382T>C NP_001394818.1:p.Val1461Ala missense NM_001407894.1:c.4379T>C NP_001394823.1:p.Val1460Ala missense NM_001407895.1:c.4379T>C NP_001394824.1:p.Val1460Ala missense NM_001407896.1:c.4379T>C NP_001394825.1:p.Val1460Ala missense NM_001407897.1:c.4379T>C NP_001394826.1:p.Val1460Ala missense NM_001407898.1:c.4379T>C NP_001394827.1:p.Val1460Ala missense NM_001407899.1:c.4379T>C NP_001394828.1:p.Val1460Ala missense NM_001407900.1:c.4379T>C NP_001394829.1:p.Val1460Ala missense NM_001407902.1:c.4379T>C NP_001394831.1:p.Val1460Ala missense NM_001407904.1:c.4379T>C NP_001394833.1:p.Val1460Ala missense NM_001407906.1:c.4379T>C NP_001394835.1:p.Val1460Ala missense NM_001407907.1:c.4379T>C NP_001394836.1:p.Val1460Ala missense NM_001407908.1:c.4379T>C NP_001394837.1:p.Val1460Ala missense NM_001407909.1:c.4379T>C NP_001394838.1:p.Val1460Ala missense NM_001407910.1:c.4379T>C NP_001394839.1:p.Val1460Ala missense NM_001407915.1:c.4376T>C NP_001394844.1:p.Val1459Ala missense NM_001407916.1:c.4376T>C NP_001394845.1:p.Val1459Ala missense NM_001407917.1:c.4376T>C NP_001394846.1:p.Val1459Ala missense NM_001407918.1:c.4376T>C NP_001394847.1:p.Val1459Ala missense NM_001407919.1:c.4469T>C NP_001394848.1:p.Val1490Ala missense NM_001407920.1:c.4328T>C NP_001394849.1:p.Val1443Ala missense NM_001407921.1:c.4328T>C NP_001394850.1:p.Val1443Ala missense NM_001407922.1:c.4328T>C NP_001394851.1:p.Val1443Ala missense NM_001407923.1:c.4328T>C NP_001394852.1:p.Val1443Ala missense NM_001407924.1:c.4328T>C NP_001394853.1:p.Val1443Ala missense NM_001407925.1:c.4328T>C NP_001394854.1:p.Val1443Ala missense NM_001407926.1:c.4328T>C NP_001394855.1:p.Val1443Ala missense NM_001407927.1:c.4325T>C NP_001394856.1:p.Val1442Ala missense NM_001407928.1:c.4325T>C NP_001394857.1:p.Val1442Ala missense NM_001407929.1:c.4325T>C NP_001394858.1:p.Val1442Ala missense NM_001407930.1:c.4325T>C NP_001394859.1:p.Val1442Ala missense NM_001407931.1:c.4325T>C NP_001394860.1:p.Val1442Ala missense NM_001407932.1:c.4325T>C NP_001394861.1:p.Val1442Ala missense NM_001407933.1:c.4325T>C NP_001394862.1:p.Val1442Ala missense NM_001407934.1:c.4322T>C NP_001394863.1:p.Val1441Ala missense NM_001407935.1:c.4322T>C NP_001394864.1:p.Val1441Ala missense NM_001407936.1:c.4322T>C NP_001394865.1:p.Val1441Ala missense NM_001407937.1:c.4469T>C NP_001394866.1:p.Val1490Ala missense NM_001407938.1:c.4469T>C NP_001394867.1:p.Val1490Ala missense NM_001407939.1:c.4466T>C NP_001394868.1:p.Val1489Ala missense NM_001407940.1:c.4466T>C NP_001394869.1:p.Val1489Ala missense NM_001407941.1:c.4463T>C NP_001394870.1:p.Val1488Ala missense NM_001407942.1:c.4451T>C NP_001394871.1:p.Val1484Ala missense NM_001407943.1:c.4448T>C NP_001394872.1:p.Val1483Ala missense NM_001407944.1:c.4448T>C NP_001394873.1:p.Val1483Ala missense NM_001407945.1:c.4448T>C NP_001394874.1:p.Val1483Ala missense NM_001407946.1:c.4259T>C NP_001394875.1:p.Val1420Ala missense NM_001407947.1:c.4259T>C NP_001394876.1:p.Val1420Ala missense NM_001407948.1:c.4259T>C NP_001394877.1:p.Val1420Ala missense NM_001407949.1:c.4259T>C NP_001394878.1:p.Val1420Ala missense NM_001407950.1:c.4256T>C NP_001394879.1:p.Val1419Ala missense NM_001407951.1:c.4256T>C NP_001394880.1:p.Val1419Ala missense NM_001407952.1:c.4256T>C NP_001394881.1:p.Val1419Ala missense NM_001407953.1:c.4256T>C NP_001394882.1:p.Val1419Ala missense NM_001407954.1:c.4256T>C NP_001394883.1:p.Val1419Ala missense NM_001407955.1:c.4256T>C NP_001394884.1:p.Val1419Ala missense NM_001407956.1:c.4253T>C NP_001394885.1:p.Val1418Ala missense NM_001407957.1:c.4253T>C NP_001394886.1:p.Val1418Ala missense NM_001407958.1:c.4253T>C NP_001394887.1:p.Val1418Ala missense NM_001407959.1:c.4211T>C NP_001394888.1:p.Val1404Ala missense NM_001407960.1:c.4208T>C NP_001394889.1:p.Val1403Ala missense NM_001407962.1:c.4208T>C NP_001394891.1:p.Val1403Ala missense NM_001407963.1:c.4205T>C NP_001394892.1:p.Val1402Ala missense NM_001407965.1:c.4085T>C NP_001394894.1:p.Val1362Ala missense NM_001407966.1:c.3704T>C NP_001394895.1:p.Val1235Ala missense NM_001407967.1:c.3701T>C NP_001394896.1:p.Val1234Ala missense NM_001407968.1:c.1988T>C NP_001394897.1:p.Val663Ala missense NM_001407969.1:c.1985T>C NP_001394898.1:p.Val662Ala missense NM_001407970.1:c.1349T>C NP_001394899.1:p.Val450Ala missense NM_001407971.1:c.1349T>C NP_001394900.1:p.Val450Ala missense NM_001407972.1:c.1346T>C NP_001394901.1:p.Val449Ala missense NM_001407973.1:c.1283T>C NP_001394902.1:p.Val428Ala missense NM_001407974.1:c.1283T>C NP_001394903.1:p.Val428Ala missense NM_001407975.1:c.1283T>C NP_001394904.1:p.Val428Ala missense NM_001407976.1:c.1283T>C NP_001394905.1:p.Val428Ala missense NM_001407977.1:c.1283T>C NP_001394906.1:p.Val428Ala missense NM_001407978.1:c.1283T>C NP_001394907.1:p.Val428Ala missense NM_001407979.1:c.1280T>C NP_001394908.1:p.Val427Ala missense NM_001407980.1:c.1280T>C NP_001394909.1:p.Val427Ala missense NM_001407981.1:c.1280T>C NP_001394910.1:p.Val427Ala missense NM_001407982.1:c.1280T>C NP_001394911.1:p.Val427Ala missense NM_001407983.1:c.1280T>C NP_001394912.1:p.Val427Ala missense NM_001407984.1:c.1280T>C NP_001394913.1:p.Val427Ala missense NM_001407985.1:c.1280T>C NP_001394914.1:p.Val427Ala missense NM_001407986.1:c.1280T>C NP_001394915.1:p.Val427Ala missense NM_001407990.1:c.1280T>C NP_001394919.1:p.Val427Ala missense NM_001407991.1:c.1280T>C NP_001394920.1:p.Val427Ala missense NM_001407992.1:c.1280T>C NP_001394921.1:p.Val427Ala missense NM_001407993.1:c.1280T>C NP_001394922.1:p.Val427Ala missense NM_001408392.1:c.1277T>C NP_001395321.1:p.Val426Ala missense NM_001408396.1:c.1277T>C NP_001395325.1:p.Val426Ala missense NM_001408397.1:c.1277T>C NP_001395326.1:p.Val426Ala missense NM_001408398.1:c.1277T>C NP_001395327.1:p.Val426Ala missense NM_001408399.1:c.1277T>C NP_001395328.1:p.Val426Ala missense NM_001408400.1:c.1277T>C NP_001395329.1:p.Val426Ala missense NM_001408401.1:c.1277T>C NP_001395330.1:p.Val426Ala missense NM_001408402.1:c.1277T>C NP_001395331.1:p.Val426Ala missense NM_001408403.1:c.1277T>C NP_001395332.1:p.Val426Ala missense NM_001408404.1:c.1277T>C NP_001395333.1:p.Val426Ala missense NM_001408406.1:c.1274T>C NP_001395335.1:p.Val425Ala missense NM_001408407.1:c.1274T>C NP_001395336.1:p.Val425Ala missense NM_001408408.1:c.1274T>C NP_001395337.1:p.Val425Ala missense NM_001408409.1:c.1271T>C NP_001395338.1:p.Val424Ala missense NM_001408410.1:c.1208T>C NP_001395339.1:p.Val403Ala missense NM_001408411.1:c.1205T>C NP_001395340.1:p.Val402Ala missense NM_001408412.1:c.1202T>C NP_001395341.1:p.Val401Ala missense NM_001408413.1:c.1202T>C NP_001395342.1:p.Val401Ala missense NM_001408414.1:c.1202T>C NP_001395343.1:p.Val401Ala missense NM_001408415.1:c.1202T>C NP_001395344.1:p.Val401Ala missense NM_001408416.1:c.1202T>C NP_001395345.1:p.Val401Ala missense NM_001408418.1:c.1166T>C NP_001395347.1:p.Val389Ala missense NM_001408419.1:c.1166T>C NP_001395348.1:p.Val389Ala missense NM_001408420.1:c.1166T>C NP_001395349.1:p.Val389Ala missense NM_001408421.1:c.1163T>C NP_001395350.1:p.Val388Ala missense NM_001408422.1:c.1163T>C NP_001395351.1:p.Val388Ala missense NM_001408423.1:c.1163T>C NP_001395352.1:p.Val388Ala missense NM_001408424.1:c.1163T>C NP_001395353.1:p.Val388Ala missense NM_001408425.1:c.1160T>C NP_001395354.1:p.Val387Ala missense NM_001408426.1:c.1160T>C NP_001395355.1:p.Val387Ala missense NM_001408427.1:c.1160T>C NP_001395356.1:p.Val387Ala missense NM_001408428.1:c.1160T>C NP_001395357.1:p.Val387Ala missense NM_001408429.1:c.1160T>C NP_001395358.1:p.Val387Ala missense NM_001408430.1:c.1160T>C NP_001395359.1:p.Val387Ala missense NM_001408431.1:c.1160T>C NP_001395360.1:p.Val387Ala missense NM_001408432.1:c.1157T>C NP_001395361.1:p.Val386Ala missense NM_001408433.1:c.1157T>C NP_001395362.1:p.Val386Ala missense NM_001408434.1:c.1157T>C NP_001395363.1:p.Val386Ala missense NM_001408435.1:c.1157T>C NP_001395364.1:p.Val386Ala missense NM_001408436.1:c.1157T>C NP_001395365.1:p.Val386Ala missense NM_001408437.1:c.1157T>C NP_001395366.1:p.Val386Ala missense NM_001408438.1:c.1157T>C NP_001395367.1:p.Val386Ala missense NM_001408439.1:c.1157T>C NP_001395368.1:p.Val386Ala missense NM_001408440.1:c.1157T>C NP_001395369.1:p.Val386Ala missense NM_001408441.1:c.1157T>C NP_001395370.1:p.Val386Ala missense NM_001408442.1:c.1157T>C NP_001395371.1:p.Val386Ala missense NM_001408443.1:c.1157T>C NP_001395372.1:p.Val386Ala missense NM_001408444.1:c.1157T>C NP_001395373.1:p.Val386Ala missense NM_001408445.1:c.1154T>C NP_001395374.1:p.Val385Ala missense NM_001408446.1:c.1154T>C NP_001395375.1:p.Val385Ala missense NM_001408447.1:c.1154T>C NP_001395376.1:p.Val385Ala missense NM_001408448.1:c.1154T>C NP_001395377.1:p.Val385Ala missense NM_001408450.1:c.1154T>C NP_001395379.1:p.Val385Ala missense NM_001408451.1:c.1148T>C NP_001395380.1:p.Val383Ala missense NM_001408452.1:c.1142T>C NP_001395381.1:p.Val381Ala missense NM_001408453.1:c.1142T>C NP_001395382.1:p.Val381Ala missense NM_001408454.1:c.1142T>C NP_001395383.1:p.Val381Ala missense NM_001408455.1:c.1142T>C NP_001395384.1:p.Val381Ala missense NM_001408456.1:c.1142T>C NP_001395385.1:p.Val381Ala missense NM_001408457.1:c.1142T>C NP_001395386.1:p.Val381Ala missense NM_001408458.1:c.1139T>C NP_001395387.1:p.Val380Ala missense NM_001408459.1:c.1139T>C NP_001395388.1:p.Val380Ala missense NM_001408460.1:c.1139T>C NP_001395389.1:p.Val380Ala missense NM_001408461.1:c.1139T>C NP_001395390.1:p.Val380Ala missense NM_001408462.1:c.1139T>C NP_001395391.1:p.Val380Ala missense NM_001408463.1:c.1139T>C NP_001395392.1:p.Val380Ala missense NM_001408464.1:c.1139T>C NP_001395393.1:p.Val380Ala missense NM_001408465.1:c.1139T>C NP_001395394.1:p.Val380Ala missense NM_001408466.1:c.1139T>C NP_001395395.1:p.Val380Ala missense NM_001408467.1:c.1139T>C NP_001395396.1:p.Val380Ala missense NM_001408468.1:c.1136T>C NP_001395397.1:p.Val379Ala missense NM_001408469.1:c.1136T>C NP_001395398.1:p.Val379Ala missense NM_001408470.1:c.1136T>C NP_001395399.1:p.Val379Ala missense NM_001408472.1:c.1280T>C NP_001395401.1:p.Val427Ala missense NM_001408473.1:c.1277T>C NP_001395402.1:p.Val426Ala missense NM_001408474.1:c.1082T>C NP_001395403.1:p.Val361Ala missense NM_001408475.1:c.1079T>C NP_001395404.1:p.Val360Ala missense NM_001408476.1:c.1079T>C NP_001395405.1:p.Val360Ala missense NM_001408478.1:c.1073T>C NP_001395407.1:p.Val358Ala missense NM_001408479.1:c.1073T>C NP_001395408.1:p.Val358Ala missense NM_001408480.1:c.1073T>C NP_001395409.1:p.Val358Ala missense NM_001408481.1:c.1070T>C NP_001395410.1:p.Val357Ala missense NM_001408482.1:c.1070T>C NP_001395411.1:p.Val357Ala missense NM_001408483.1:c.1070T>C NP_001395412.1:p.Val357Ala missense NM_001408484.1:c.1070T>C NP_001395413.1:p.Val357Ala missense NM_001408485.1:c.1070T>C NP_001395414.1:p.Val357Ala missense NM_001408489.1:c.1070T>C NP_001395418.1:p.Val357Ala missense NM_001408490.1:c.1070T>C NP_001395419.1:p.Val357Ala missense NM_001408491.1:c.1070T>C NP_001395420.1:p.Val357Ala missense NM_001408492.1:c.1067T>C NP_001395421.1:p.Val356Ala missense NM_001408493.1:c.1067T>C NP_001395422.1:p.Val356Ala missense NM_001408494.1:c.1043T>C NP_001395423.1:p.Val348Ala missense NM_001408495.1:c.1037T>C NP_001395424.1:p.Val346Ala missense NM_001408496.1:c.1019T>C NP_001395425.1:p.Val340Ala missense NM_001408497.1:c.1019T>C NP_001395426.1:p.Val340Ala missense NM_001408498.1:c.1019T>C NP_001395427.1:p.Val340Ala missense NM_001408499.1:c.1019T>C NP_001395428.1:p.Val340Ala missense NM_001408500.1:c.1019T>C NP_001395429.1:p.Val340Ala missense NM_001408501.1:c.1019T>C NP_001395430.1:p.Val340Ala missense NM_001408502.1:c.1016T>C NP_001395431.1:p.Val339Ala missense NM_001408503.1:c.1016T>C NP_001395432.1:p.Val339Ala missense NM_001408504.1:c.1016T>C NP_001395433.1:p.Val339Ala missense NM_001408505.1:c.1013T>C NP_001395434.1:p.Val338Ala missense NM_001408506.1:c.956T>C NP_001395435.1:p.Val319Ala missense NM_001408507.1:c.953T>C NP_001395436.1:p.Val318Ala missense NM_001408508.1:c.944T>C NP_001395437.1:p.Val315Ala missense NM_001408509.1:c.941T>C NP_001395438.1:p.Val314Ala missense NM_001408510.1:c.902T>C NP_001395439.1:p.Val301Ala missense NM_001408511.1:c.899T>C NP_001395440.1:p.Val300Ala missense NM_001408512.1:c.779T>C NP_001395441.1:p.Val260Ala missense NM_007297.4:c.4451T>C NP_009228.2:p.Val1484Ala missense NM_007298.4:c.1280T>C NP_009229.2:p.Val427Ala missense NM_007299.4:c.1280T>C NP_009230.2:p.Val427Ala missense NM_007300.4:c.4655T>C NP_009231.2:p.Val1552Ala missense NM_007304.2:c.1280T>C NP_009235.2:p.Val427Ala missense NR_027676.2:n.4769T>C non-coding transcript variant NC_000017.11:g.43074414A>G NC_000017.10:g.41226431A>G NG_005905.2:g.143570T>C LRG_292:g.143570T>C LRG_292t1:c.4592T>C LRG_292p1:p.Val1531Ala - Protein change
- V1234A, V1235A, V1362A, V1402A, V1403A, V1404A, V1418A, V1419A, V1420A, V1441A, V1442A, V1443A, V1459A, V1460A, V1461A, V1462A, V1464A, V1482A, V1483A, V1484A, V1487A, V1488A, V1489A, V1490A, V1503A, V1504A, V1505A, V1511A, V1512A, V1526A, V1527A, V1528A, V1529A, V1530A, V1531A, V1551A, V1552A, V1553A, V260A, V300A, V301A, V314A, V315A, V318A, V319A, V338A, V339A, V340A, V346A, V348A, V356A, V357A, V358A, V360A, V361A, V379A, V380A, V381A, V383A, V385A, V386A, V387A, V388A, V389A, V401A, V402A, V403A, V424A, V425A, V426A, V427A, V428A, V449A, V450A, V662A, V663A
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074413: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.
- -
- 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 |
13041 | 14847 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 13, 2023 | RCV002301400.4 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Oct 13, 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: SCV002590381.3
First in ClinVar: Nov 05, 2022 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1531 of the BRCA1 protein (p.Val1531Ala). … (more)
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1531 of the BRCA1 protein (p.Val1531Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1715651). 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. 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)
|
Comment:
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:
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1531 of the BRCA1 protein (p.Val1531Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1715651). 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. 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.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.