The p.V1333A variant (also known as c.3998T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3998. The valine at codon 1333 is replaced by alanine, an amino acid with similar 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.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3998T>C (p.Val1333Ala)
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.
(6)
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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.
Conflicting classifications of pathogenicity
Uncertain significance(3); Likely benign(1)
Uncertain significance(3); Likely benign(1)
6
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.3998T>C (p.Val1333Ala)
Variation ID: 431258 Accession: VCV000431258.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091533 (GRCh38) [ NCBI UCSC ] 17: 41243550 (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 Aug 7, 2017 May 1, 2024 Mar 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3998T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Val1333Ala missense NM_001407571.1:c.3785T>C NP_001394500.1:p.Val1262Ala missense NM_001407581.1:c.3998T>C NP_001394510.1:p.Val1333Ala missense NM_001407582.1:c.3998T>C NP_001394511.1:p.Val1333Ala missense NM_001407583.1:c.3998T>C NP_001394512.1:p.Val1333Ala missense NM_001407585.1:c.3998T>C NP_001394514.1:p.Val1333Ala missense NM_001407587.1:c.3995T>C NP_001394516.1:p.Val1332Ala missense NM_001407590.1:c.3995T>C NP_001394519.1:p.Val1332Ala missense NM_001407591.1:c.3995T>C NP_001394520.1:p.Val1332Ala missense NM_001407593.1:c.3998T>C NP_001394522.1:p.Val1333Ala missense NM_001407594.1:c.3998T>C NP_001394523.1:p.Val1333Ala missense NM_001407596.1:c.3998T>C NP_001394525.1:p.Val1333Ala missense NM_001407597.1:c.3998T>C NP_001394526.1:p.Val1333Ala missense NM_001407598.1:c.3998T>C NP_001394527.1:p.Val1333Ala missense NM_001407602.1:c.3998T>C NP_001394531.1:p.Val1333Ala missense NM_001407603.1:c.3998T>C NP_001394532.1:p.Val1333Ala missense NM_001407605.1:c.3998T>C NP_001394534.1:p.Val1333Ala missense NM_001407610.1:c.3995T>C NP_001394539.1:p.Val1332Ala missense NM_001407611.1:c.3995T>C NP_001394540.1:p.Val1332Ala missense NM_001407612.1:c.3995T>C NP_001394541.1:p.Val1332Ala missense NM_001407613.1:c.3995T>C NP_001394542.1:p.Val1332Ala missense NM_001407614.1:c.3995T>C NP_001394543.1:p.Val1332Ala missense NM_001407615.1:c.3995T>C NP_001394544.1:p.Val1332Ala missense NM_001407616.1:c.3998T>C NP_001394545.1:p.Val1333Ala missense NM_001407617.1:c.3998T>C NP_001394546.1:p.Val1333Ala missense NM_001407618.1:c.3998T>C NP_001394547.1:p.Val1333Ala missense NM_001407619.1:c.3998T>C NP_001394548.1:p.Val1333Ala missense NM_001407620.1:c.3998T>C NP_001394549.1:p.Val1333Ala missense NM_001407621.1:c.3998T>C NP_001394550.1:p.Val1333Ala missense NM_001407622.1:c.3998T>C NP_001394551.1:p.Val1333Ala missense NM_001407623.1:c.3998T>C NP_001394552.1:p.Val1333Ala missense NM_001407624.1:c.3998T>C NP_001394553.1:p.Val1333Ala missense NM_001407625.1:c.3998T>C NP_001394554.1:p.Val1333Ala missense NM_001407626.1:c.3998T>C NP_001394555.1:p.Val1333Ala missense NM_001407627.1:c.3995T>C NP_001394556.1:p.Val1332Ala missense NM_001407628.1:c.3995T>C NP_001394557.1:p.Val1332Ala missense NM_001407629.1:c.3995T>C NP_001394558.1:p.Val1332Ala missense NM_001407630.1:c.3995T>C NP_001394559.1:p.Val1332Ala missense NM_001407631.1:c.3995T>C NP_001394560.1:p.Val1332Ala missense NM_001407632.1:c.3995T>C NP_001394561.1:p.Val1332Ala missense NM_001407633.1:c.3995T>C NP_001394562.1:p.Val1332Ala missense NM_001407634.1:c.3995T>C NP_001394563.1:p.Val1332Ala missense NM_001407635.1:c.3995T>C NP_001394564.1:p.Val1332Ala missense NM_001407636.1:c.3995T>C NP_001394565.1:p.Val1332Ala missense NM_001407637.1:c.3995T>C NP_001394566.1:p.Val1332Ala missense NM_001407638.1:c.3995T>C NP_001394567.1:p.Val1332Ala missense NM_001407639.1:c.3998T>C NP_001394568.1:p.Val1333Ala missense NM_001407640.1:c.3998T>C NP_001394569.1:p.Val1333Ala missense NM_001407641.1:c.3998T>C NP_001394570.1:p.Val1333Ala missense NM_001407642.1:c.3998T>C NP_001394571.1:p.Val1333Ala missense NM_001407644.1:c.3995T>C NP_001394573.1:p.Val1332Ala missense NM_001407645.1:c.3995T>C NP_001394574.1:p.Val1332Ala missense NM_001407646.1:c.3989T>C NP_001394575.1:p.Val1330Ala missense NM_001407647.1:c.3989T>C NP_001394576.1:p.Val1330Ala missense NM_001407648.1:c.3875T>C NP_001394577.1:p.Val1292Ala missense NM_001407649.1:c.3872T>C NP_001394578.1:p.Val1291Ala missense NM_001407652.1:c.3998T>C NP_001394581.1:p.Val1333Ala missense NM_001407653.1:c.3920T>C NP_001394582.1:p.Val1307Ala missense NM_001407654.1:c.3920T>C NP_001394583.1:p.Val1307Ala missense NM_001407655.1:c.3920T>C NP_001394584.1:p.Val1307Ala missense NM_001407656.1:c.3920T>C NP_001394585.1:p.Val1307Ala missense NM_001407657.1:c.3920T>C NP_001394586.1:p.Val1307Ala missense NM_001407658.1:c.3920T>C NP_001394587.1:p.Val1307Ala missense NM_001407659.1:c.3917T>C NP_001394588.1:p.Val1306Ala missense NM_001407660.1:c.3917T>C NP_001394589.1:p.Val1306Ala missense NM_001407661.1:c.3917T>C NP_001394590.1:p.Val1306Ala missense NM_001407662.1:c.3917T>C NP_001394591.1:p.Val1306Ala missense NM_001407663.1:c.3920T>C NP_001394592.1:p.Val1307Ala missense NM_001407664.1:c.3875T>C NP_001394593.1:p.Val1292Ala missense NM_001407665.1:c.3875T>C NP_001394594.1:p.Val1292Ala missense NM_001407666.1:c.3875T>C NP_001394595.1:p.Val1292Ala missense NM_001407667.1:c.3875T>C NP_001394596.1:p.Val1292Ala missense NM_001407668.1:c.3875T>C NP_001394597.1:p.Val1292Ala missense NM_001407669.1:c.3875T>C NP_001394598.1:p.Val1292Ala missense NM_001407670.1:c.3872T>C NP_001394599.1:p.Val1291Ala missense NM_001407671.1:c.3872T>C NP_001394600.1:p.Val1291Ala missense NM_001407672.1:c.3872T>C NP_001394601.1:p.Val1291Ala missense NM_001407673.1:c.3872T>C NP_001394602.1:p.Val1291Ala missense NM_001407674.1:c.3875T>C NP_001394603.1:p.Val1292Ala missense NM_001407675.1:c.3875T>C NP_001394604.1:p.Val1292Ala missense NM_001407676.1:c.3875T>C NP_001394605.1:p.Val1292Ala missense NM_001407677.1:c.3875T>C NP_001394606.1:p.Val1292Ala missense NM_001407678.1:c.3875T>C NP_001394607.1:p.Val1292Ala missense NM_001407679.1:c.3875T>C NP_001394608.1:p.Val1292Ala missense NM_001407680.1:c.3875T>C NP_001394609.1:p.Val1292Ala missense NM_001407681.1:c.3875T>C NP_001394610.1:p.Val1292Ala missense NM_001407682.1:c.3875T>C NP_001394611.1:p.Val1292Ala missense NM_001407683.1:c.3875T>C NP_001394612.1:p.Val1292Ala missense NM_001407684.1:c.3998T>C NP_001394613.1:p.Val1333Ala missense NM_001407685.1:c.3872T>C NP_001394614.1:p.Val1291Ala missense NM_001407686.1:c.3872T>C NP_001394615.1:p.Val1291Ala missense NM_001407687.1:c.3872T>C NP_001394616.1:p.Val1291Ala missense NM_001407688.1:c.3872T>C NP_001394617.1:p.Val1291Ala missense NM_001407689.1:c.3872T>C NP_001394618.1:p.Val1291Ala missense NM_001407690.1:c.3872T>C NP_001394619.1:p.Val1291Ala missense NM_001407691.1:c.3872T>C NP_001394620.1:p.Val1291Ala missense NM_001407692.1:c.3857T>C NP_001394621.1:p.Val1286Ala missense NM_001407694.1:c.3857T>C NP_001394623.1:p.Val1286Ala missense NM_001407695.1:c.3857T>C NP_001394624.1:p.Val1286Ala missense NM_001407696.1:c.3857T>C NP_001394625.1:p.Val1286Ala missense NM_001407697.1:c.3857T>C NP_001394626.1:p.Val1286Ala missense NM_001407698.1:c.3857T>C NP_001394627.1:p.Val1286Ala missense NM_001407724.1:c.3857T>C NP_001394653.1:p.Val1286Ala missense NM_001407725.1:c.3857T>C NP_001394654.1:p.Val1286Ala missense NM_001407726.1:c.3857T>C NP_001394655.1:p.Val1286Ala missense NM_001407727.1:c.3857T>C NP_001394656.1:p.Val1286Ala missense NM_001407728.1:c.3857T>C NP_001394657.1:p.Val1286Ala missense NM_001407729.1:c.3857T>C NP_001394658.1:p.Val1286Ala missense NM_001407730.1:c.3857T>C NP_001394659.1:p.Val1286Ala missense NM_001407731.1:c.3857T>C NP_001394660.1:p.Val1286Ala missense NM_001407732.1:c.3857T>C NP_001394661.1:p.Val1286Ala missense NM_001407733.1:c.3857T>C NP_001394662.1:p.Val1286Ala missense NM_001407734.1:c.3857T>C NP_001394663.1:p.Val1286Ala missense NM_001407735.1:c.3857T>C NP_001394664.1:p.Val1286Ala missense NM_001407736.1:c.3857T>C NP_001394665.1:p.Val1286Ala missense NM_001407737.1:c.3857T>C NP_001394666.1:p.Val1286Ala missense NM_001407738.1:c.3857T>C NP_001394667.1:p.Val1286Ala missense NM_001407739.1:c.3857T>C NP_001394668.1:p.Val1286Ala missense NM_001407740.1:c.3854T>C NP_001394669.1:p.Val1285Ala missense NM_001407741.1:c.3854T>C NP_001394670.1:p.Val1285Ala missense NM_001407742.1:c.3854T>C NP_001394671.1:p.Val1285Ala missense NM_001407743.1:c.3854T>C NP_001394672.1:p.Val1285Ala missense NM_001407744.1:c.3854T>C NP_001394673.1:p.Val1285Ala missense NM_001407745.1:c.3854T>C NP_001394674.1:p.Val1285Ala missense NM_001407746.1:c.3854T>C NP_001394675.1:p.Val1285Ala missense NM_001407747.1:c.3854T>C NP_001394676.1:p.Val1285Ala missense NM_001407748.1:c.3854T>C NP_001394677.1:p.Val1285Ala missense NM_001407749.1:c.3854T>C NP_001394678.1:p.Val1285Ala missense NM_001407750.1:c.3857T>C NP_001394679.1:p.Val1286Ala missense NM_001407751.1:c.3857T>C NP_001394680.1:p.Val1286Ala missense NM_001407752.1:c.3857T>C NP_001394681.1:p.Val1286Ala missense NM_001407838.1:c.3854T>C NP_001394767.1:p.Val1285Ala missense NM_001407839.1:c.3854T>C NP_001394768.1:p.Val1285Ala missense NM_001407841.1:c.3854T>C NP_001394770.1:p.Val1285Ala missense NM_001407842.1:c.3854T>C NP_001394771.1:p.Val1285Ala missense NM_001407843.1:c.3854T>C NP_001394772.1:p.Val1285Ala missense NM_001407844.1:c.3854T>C NP_001394773.1:p.Val1285Ala missense NM_001407845.1:c.3854T>C NP_001394774.1:p.Val1285Ala missense NM_001407846.1:c.3854T>C NP_001394775.1:p.Val1285Ala missense NM_001407847.1:c.3854T>C NP_001394776.1:p.Val1285Ala missense NM_001407848.1:c.3854T>C NP_001394777.1:p.Val1285Ala missense NM_001407849.1:c.3854T>C NP_001394778.1:p.Val1285Ala missense NM_001407850.1:c.3857T>C NP_001394779.1:p.Val1286Ala missense NM_001407851.1:c.3857T>C NP_001394780.1:p.Val1286Ala missense NM_001407852.1:c.3857T>C NP_001394781.1:p.Val1286Ala missense NM_001407853.1:c.3785T>C NP_001394782.1:p.Val1262Ala missense NM_001407854.1:c.3998T>C NP_001394783.1:p.Val1333Ala missense NM_001407858.1:c.3998T>C NP_001394787.1:p.Val1333Ala missense NM_001407859.1:c.3998T>C NP_001394788.1:p.Val1333Ala missense NM_001407860.1:c.3995T>C NP_001394789.1:p.Val1332Ala missense NM_001407861.1:c.3995T>C NP_001394790.1:p.Val1332Ala missense NM_001407862.1:c.3797T>C NP_001394791.1:p.Val1266Ala missense NM_001407863.1:c.3875T>C NP_001394792.1:p.Val1292Ala missense NM_001407874.1:c.3794T>C NP_001394803.1:p.Val1265Ala missense NM_001407875.1:c.3794T>C NP_001394804.1:p.Val1265Ala missense NM_001407879.1:c.3788T>C NP_001394808.1:p.Val1263Ala missense NM_001407881.1:c.3788T>C NP_001394810.1:p.Val1263Ala missense NM_001407882.1:c.3788T>C NP_001394811.1:p.Val1263Ala missense NM_001407884.1:c.3788T>C NP_001394813.1:p.Val1263Ala missense NM_001407885.1:c.3788T>C NP_001394814.1:p.Val1263Ala missense NM_001407886.1:c.3788T>C NP_001394815.1:p.Val1263Ala missense NM_001407887.1:c.3788T>C NP_001394816.1:p.Val1263Ala missense NM_001407889.1:c.3788T>C NP_001394818.1:p.Val1263Ala missense NM_001407894.1:c.3785T>C NP_001394823.1:p.Val1262Ala missense NM_001407895.1:c.3785T>C NP_001394824.1:p.Val1262Ala missense NM_001407896.1:c.3785T>C NP_001394825.1:p.Val1262Ala missense NM_001407897.1:c.3785T>C NP_001394826.1:p.Val1262Ala missense NM_001407898.1:c.3785T>C NP_001394827.1:p.Val1262Ala missense NM_001407899.1:c.3785T>C NP_001394828.1:p.Val1262Ala missense NM_001407900.1:c.3788T>C NP_001394829.1:p.Val1263Ala missense NM_001407902.1:c.3788T>C NP_001394831.1:p.Val1263Ala missense NM_001407904.1:c.3788T>C NP_001394833.1:p.Val1263Ala missense NM_001407906.1:c.3788T>C NP_001394835.1:p.Val1263Ala missense NM_001407907.1:c.3788T>C NP_001394836.1:p.Val1263Ala missense NM_001407908.1:c.3788T>C NP_001394837.1:p.Val1263Ala missense NM_001407909.1:c.3788T>C NP_001394838.1:p.Val1263Ala missense NM_001407910.1:c.3788T>C NP_001394839.1:p.Val1263Ala missense NM_001407915.1:c.3785T>C NP_001394844.1:p.Val1262Ala missense NM_001407916.1:c.3785T>C NP_001394845.1:p.Val1262Ala missense NM_001407917.1:c.3785T>C NP_001394846.1:p.Val1262Ala missense NM_001407918.1:c.3785T>C NP_001394847.1:p.Val1262Ala missense NM_001407919.1:c.3875T>C NP_001394848.1:p.Val1292Ala missense NM_001407920.1:c.3734T>C NP_001394849.1:p.Val1245Ala missense NM_001407921.1:c.3734T>C NP_001394850.1:p.Val1245Ala missense NM_001407922.1:c.3734T>C NP_001394851.1:p.Val1245Ala missense NM_001407923.1:c.3734T>C NP_001394852.1:p.Val1245Ala missense NM_001407924.1:c.3734T>C NP_001394853.1:p.Val1245Ala missense NM_001407925.1:c.3734T>C NP_001394854.1:p.Val1245Ala missense NM_001407926.1:c.3734T>C NP_001394855.1:p.Val1245Ala missense NM_001407927.1:c.3734T>C NP_001394856.1:p.Val1245Ala missense NM_001407928.1:c.3734T>C NP_001394857.1:p.Val1245Ala missense NM_001407929.1:c.3734T>C NP_001394858.1:p.Val1245Ala missense NM_001407930.1:c.3731T>C NP_001394859.1:p.Val1244Ala missense NM_001407931.1:c.3731T>C NP_001394860.1:p.Val1244Ala missense NM_001407932.1:c.3731T>C NP_001394861.1:p.Val1244Ala missense NM_001407933.1:c.3734T>C NP_001394862.1:p.Val1245Ala missense NM_001407934.1:c.3731T>C NP_001394863.1:p.Val1244Ala missense NM_001407935.1:c.3734T>C NP_001394864.1:p.Val1245Ala missense NM_001407936.1:c.3731T>C NP_001394865.1:p.Val1244Ala missense NM_001407937.1:c.3875T>C NP_001394866.1:p.Val1292Ala missense NM_001407938.1:c.3875T>C NP_001394867.1:p.Val1292Ala missense NM_001407939.1:c.3875T>C NP_001394868.1:p.Val1292Ala missense NM_001407940.1:c.3872T>C NP_001394869.1:p.Val1291Ala missense NM_001407941.1:c.3872T>C NP_001394870.1:p.Val1291Ala missense NM_001407942.1:c.3857T>C NP_001394871.1:p.Val1286Ala missense NM_001407943.1:c.3854T>C NP_001394872.1:p.Val1285Ala missense NM_001407944.1:c.3857T>C NP_001394873.1:p.Val1286Ala missense NM_001407945.1:c.3857T>C NP_001394874.1:p.Val1286Ala missense NM_001407946.1:c.3665T>C NP_001394875.1:p.Val1222Ala missense NM_001407947.1:c.3665T>C NP_001394876.1:p.Val1222Ala missense NM_001407948.1:c.3665T>C NP_001394877.1:p.Val1222Ala missense NM_001407949.1:c.3665T>C NP_001394878.1:p.Val1222Ala missense NM_001407950.1:c.3665T>C NP_001394879.1:p.Val1222Ala missense NM_001407951.1:c.3665T>C NP_001394880.1:p.Val1222Ala missense NM_001407952.1:c.3665T>C NP_001394881.1:p.Val1222Ala missense NM_001407953.1:c.3665T>C NP_001394882.1:p.Val1222Ala missense NM_001407954.1:c.3662T>C NP_001394883.1:p.Val1221Ala missense NM_001407955.1:c.3662T>C NP_001394884.1:p.Val1221Ala missense NM_001407956.1:c.3662T>C NP_001394885.1:p.Val1221Ala missense NM_001407957.1:c.3665T>C NP_001394886.1:p.Val1222Ala missense NM_001407958.1:c.3662T>C NP_001394887.1:p.Val1221Ala missense NM_001407959.1:c.3617T>C NP_001394888.1:p.Val1206Ala missense NM_001407960.1:c.3617T>C NP_001394889.1:p.Val1206Ala missense NM_001407962.1:c.3614T>C NP_001394891.1:p.Val1205Ala missense NM_001407963.1:c.3617T>C NP_001394892.1:p.Val1206Ala missense NM_001407964.1:c.3854T>C NP_001394893.1:p.Val1285Ala missense NM_001407965.1:c.3494T>C NP_001394894.1:p.Val1165Ala missense NM_001407966.1:c.3110T>C NP_001394895.1:p.Val1037Ala missense NM_001407967.1:c.3110T>C NP_001394896.1:p.Val1037Ala missense NM_001407968.1:c.1394T>C NP_001394897.1:p.Val465Ala missense NM_001407969.1:c.1394T>C NP_001394898.1:p.Val465Ala missense NM_001407970.1:c.788-501T>C intron variant NM_001407971.1:c.788-501T>C intron variant NM_001407972.1:c.785-501T>C intron variant NM_001407973.1:c.788-501T>C intron variant NM_001407974.1:c.788-501T>C intron variant NM_001407975.1:c.788-501T>C intron variant NM_001407976.1:c.788-501T>C intron variant NM_001407977.1:c.788-501T>C intron variant NM_001407978.1:c.788-501T>C intron variant NM_001407979.1:c.788-501T>C intron variant NM_001407980.1:c.788-501T>C intron variant NM_001407981.1:c.788-501T>C intron variant NM_001407982.1:c.788-501T>C intron variant NM_001407983.1:c.788-501T>C intron variant NM_001407984.1:c.785-501T>C intron variant NM_001407985.1:c.785-501T>C intron variant NM_001407986.1:c.785-501T>C intron variant NM_001407990.1:c.788-501T>C intron variant NM_001407991.1:c.785-501T>C intron variant NM_001407992.1:c.785-501T>C intron variant NM_001407993.1:c.788-501T>C intron variant NM_001408392.1:c.785-501T>C intron variant NM_001408396.1:c.785-501T>C intron variant NM_001408397.1:c.785-501T>C intron variant NM_001408398.1:c.785-501T>C intron variant NM_001408399.1:c.785-501T>C intron variant NM_001408400.1:c.785-501T>C intron variant NM_001408401.1:c.785-501T>C intron variant NM_001408402.1:c.785-501T>C intron variant NM_001408403.1:c.788-501T>C intron variant NM_001408404.1:c.788-501T>C intron variant NM_001408406.1:c.791-510T>C intron variant NM_001408407.1:c.785-501T>C intron variant NM_001408408.1:c.779-501T>C intron variant NM_001408409.1:c.710-501T>C intron variant NM_001408410.1:c.647-501T>C intron variant NM_001408411.1:c.710-501T>C intron variant NM_001408412.1:c.710-501T>C intron variant NM_001408413.1:c.707-501T>C intron variant NM_001408414.1:c.710-501T>C intron variant NM_001408415.1:c.710-501T>C intron variant NM_001408416.1:c.707-501T>C intron variant NM_001408418.1:c.671-501T>C intron variant NM_001408419.1:c.671-501T>C intron variant NM_001408420.1:c.671-501T>C intron variant NM_001408421.1:c.668-501T>C intron variant NM_001408422.1:c.671-501T>C intron variant NM_001408423.1:c.671-501T>C intron variant NM_001408424.1:c.668-501T>C intron variant NM_001408425.1:c.665-501T>C intron variant NM_001408426.1:c.665-501T>C intron variant NM_001408427.1:c.665-501T>C intron variant NM_001408428.1:c.665-501T>C intron variant NM_001408429.1:c.665-501T>C intron variant NM_001408430.1:c.665-501T>C intron variant NM_001408431.1:c.668-501T>C intron variant NM_001408432.1:c.662-501T>C intron variant NM_001408433.1:c.662-501T>C intron variant NM_001408434.1:c.662-501T>C intron variant NM_001408435.1:c.662-501T>C intron variant NM_001408436.1:c.665-501T>C intron variant NM_001408437.1:c.665-501T>C intron variant NM_001408438.1:c.665-501T>C intron variant NM_001408439.1:c.665-501T>C intron variant NM_001408440.1:c.665-501T>C intron variant NM_001408441.1:c.665-501T>C intron variant NM_001408442.1:c.665-501T>C intron variant NM_001408443.1:c.665-501T>C intron variant NM_001408444.1:c.665-501T>C intron variant NM_001408445.1:c.662-501T>C intron variant NM_001408446.1:c.662-501T>C intron variant NM_001408447.1:c.662-501T>C intron variant NM_001408448.1:c.662-501T>C intron variant NM_001408450.1:c.662-501T>C intron variant NM_001408451.1:c.653-501T>C intron variant NM_001408452.1:c.647-501T>C intron variant NM_001408453.1:c.647-501T>C intron variant NM_001408454.1:c.647-501T>C intron variant NM_001408455.1:c.647-501T>C intron variant NM_001408456.1:c.647-501T>C intron variant NM_001408457.1:c.647-501T>C intron variant NM_001408458.1:c.647-501T>C intron variant NM_001408459.1:c.647-501T>C intron variant NM_001408460.1:c.647-501T>C intron variant NM_001408461.1:c.647-501T>C intron variant NM_001408462.1:c.644-501T>C intron variant NM_001408463.1:c.644-501T>C intron variant NM_001408464.1:c.644-501T>C intron variant NM_001408465.1:c.644-501T>C intron variant NM_001408466.1:c.647-501T>C intron variant NM_001408467.1:c.647-501T>C intron variant NM_001408468.1:c.644-501T>C intron variant NM_001408469.1:c.647-501T>C intron variant NM_001408470.1:c.644-501T>C intron variant NM_001408472.1:c.788-501T>C intron variant NM_001408473.1:c.785-501T>C intron variant NM_001408474.1:c.587-501T>C intron variant NM_001408475.1:c.584-501T>C intron variant NM_001408476.1:c.587-501T>C intron variant NM_001408478.1:c.578-501T>C intron variant NM_001408479.1:c.578-501T>C intron variant NM_001408480.1:c.578-501T>C intron variant NM_001408481.1:c.578-501T>C intron variant NM_001408482.1:c.578-501T>C intron variant NM_001408483.1:c.578-501T>C intron variant NM_001408484.1:c.578-501T>C intron variant NM_001408485.1:c.578-501T>C intron variant NM_001408489.1:c.578-501T>C intron variant NM_001408490.1:c.575-501T>C intron variant NM_001408491.1:c.575-501T>C intron variant NM_001408492.1:c.578-501T>C intron variant NM_001408493.1:c.575-501T>C intron variant NM_001408494.1:c.548-501T>C intron variant NM_001408495.1:c.545-501T>C intron variant NM_001408496.1:c.524-501T>C intron variant NM_001408497.1:c.524-501T>C intron variant NM_001408498.1:c.524-501T>C intron variant NM_001408499.1:c.524-501T>C intron variant NM_001408500.1:c.524-501T>C intron variant NM_001408501.1:c.524-501T>C intron variant NM_001408502.1:c.455-501T>C intron variant NM_001408503.1:c.521-501T>C intron variant NM_001408504.1:c.521-501T>C intron variant NM_001408505.1:c.521-501T>C intron variant NM_001408506.1:c.461-501T>C intron variant NM_001408507.1:c.461-501T>C intron variant NM_001408508.1:c.452-501T>C intron variant NM_001408509.1:c.452-501T>C intron variant NM_001408510.1:c.407-501T>C intron variant NM_001408511.1:c.404-501T>C intron variant NM_001408512.1:c.284-501T>C intron variant NM_001408513.1:c.578-501T>C intron variant NM_001408514.1:c.578-501T>C intron variant NM_007297.4:c.3857T>C NP_009228.2:p.Val1286Ala missense NM_007298.4:c.788-501T>C intron variant NM_007299.4:c.788-501T>C intron variant NM_007300.4:c.3998T>C NP_009231.2:p.Val1333Ala missense NR_027676.1:n.4134T>C NC_000017.11:g.43091533A>G NC_000017.10:g.41243550A>G NG_005905.2:g.126451T>C NG_087068.1:g.515A>G LRG_292:g.126451T>C LRG_292t1:c.3998T>C LRG_292p1:p.Val1333Ala - Protein change
- V1333A, V1286A, V1245A, V1266A, V1285A, V1332A, V1037A, V1165A, V1222A, V1244A, V1307A, V1205A, V1206A, V1221A, V1263A, V1265A, V1306A, V465A, V1262A, V1291A, V1292A, V1330A
- Other names
- -
- Canonical SPDI
- NC_000017.11:43091532: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
- 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 |
13044 | 14850 | |
| 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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Mar 23, 2023 | RCV000583038.11 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 23, 2023 | RCV000530741.10 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Mar 6, 2014 | RCV000496832.2 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Mar 2, 2020 | RCV003493604.1 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Jun 06, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002622497.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.V1333A variant (also known as c.3998T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.V1333A variant (also known as c.3998T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3998. The valine at codon 1333 is replaced by alanine, an amino acid with similar 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)
|
|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003849121.1
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).
|
|
|
Uncertain significance
(Apr 12, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000688459.3
First in ClinVar: Feb 19, 2018 Last updated: Jun 22, 2020 |
|
|
|
Uncertain significance
(Mar 23, 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: SCV000635933.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This missense change has been observed in individual(s) with breast cancer (PMID: 26183948). This variant is present in population databases (no rsID available, gnomAD 0.01%). … (more)
This missense change has been observed in individual(s) with breast cancer (PMID: 26183948). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1333 of the BRCA1 protein (p.Val1333Ala). ClinVar contains an entry for this variant (Variation ID: 431258). 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. 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. (less)
|
|
|
Uncertain significance
(Mar 06, 2014)
|
no assertion criteria provided
Method: research
|
not specified
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587365.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
|
|
|
Uncertain significance
(Mar 02, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV004244019.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
Comment:
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This missense change has been observed in individual(s) with breast cancer (PMID: 26183948). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1333 of the BRCA1 protein (p.Val1333Ala). ClinVar contains an entry for this variant (Variation ID: 431258). 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. 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.
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:
The p.V1333A variant (also known as c.3998T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3998. The valine at codon 1333 is replaced by alanine, an amino acid with similar 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.
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This missense change has been observed in individual(s) with breast cancer (PMID: 26183948). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1333 of the BRCA1 protein (p.Val1333Ala). ClinVar contains an entry for this variant (Variation ID: 431258). 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. 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer patients. | Dodova RI | BMC cancer | 2015 | PMID: 26183948 |
Text-mined citations for rs1135401872 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 08, 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.