Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2267G>C (p.Arg756Thr)
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.
(2)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)
Uncertain significance(1); Likely benign(1)
2
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.2267G>C (p.Arg756Thr)
Variation ID: 966335 Accession: VCV000966335.11
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093264 (GRCh38) [ NCBI UCSC ] 17: 41245281 (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 Jul 16, 2020 Feb 20, 2024 Mar 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.2267G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Arg756Thr missense NM_001407571.1:c.2054G>C NP_001394500.1:p.Arg685Thr missense NM_001407581.1:c.2267G>C NP_001394510.1:p.Arg756Thr missense NM_001407582.1:c.2267G>C NP_001394511.1:p.Arg756Thr missense NM_001407583.1:c.2267G>C NP_001394512.1:p.Arg756Thr missense NM_001407585.1:c.2267G>C NP_001394514.1:p.Arg756Thr missense NM_001407587.1:c.2264G>C NP_001394516.1:p.Arg755Thr missense NM_001407590.1:c.2264G>C NP_001394519.1:p.Arg755Thr missense NM_001407591.1:c.2264G>C NP_001394520.1:p.Arg755Thr missense NM_001407593.1:c.2267G>C NP_001394522.1:p.Arg756Thr missense NM_001407594.1:c.2267G>C NP_001394523.1:p.Arg756Thr missense NM_001407596.1:c.2267G>C NP_001394525.1:p.Arg756Thr missense NM_001407597.1:c.2267G>C NP_001394526.1:p.Arg756Thr missense NM_001407598.1:c.2267G>C NP_001394527.1:p.Arg756Thr missense NM_001407602.1:c.2267G>C NP_001394531.1:p.Arg756Thr missense NM_001407603.1:c.2267G>C NP_001394532.1:p.Arg756Thr missense NM_001407605.1:c.2267G>C NP_001394534.1:p.Arg756Thr missense NM_001407610.1:c.2264G>C NP_001394539.1:p.Arg755Thr missense NM_001407611.1:c.2264G>C NP_001394540.1:p.Arg755Thr missense NM_001407612.1:c.2264G>C NP_001394541.1:p.Arg755Thr missense NM_001407613.1:c.2264G>C NP_001394542.1:p.Arg755Thr missense NM_001407614.1:c.2264G>C NP_001394543.1:p.Arg755Thr missense NM_001407615.1:c.2264G>C NP_001394544.1:p.Arg755Thr missense NM_001407616.1:c.2267G>C NP_001394545.1:p.Arg756Thr missense NM_001407617.1:c.2267G>C NP_001394546.1:p.Arg756Thr missense NM_001407618.1:c.2267G>C NP_001394547.1:p.Arg756Thr missense NM_001407619.1:c.2267G>C NP_001394548.1:p.Arg756Thr missense NM_001407620.1:c.2267G>C NP_001394549.1:p.Arg756Thr missense NM_001407621.1:c.2267G>C NP_001394550.1:p.Arg756Thr missense NM_001407622.1:c.2267G>C NP_001394551.1:p.Arg756Thr missense NM_001407623.1:c.2267G>C NP_001394552.1:p.Arg756Thr missense NM_001407624.1:c.2267G>C NP_001394553.1:p.Arg756Thr missense NM_001407625.1:c.2267G>C NP_001394554.1:p.Arg756Thr missense NM_001407626.1:c.2267G>C NP_001394555.1:p.Arg756Thr missense NM_001407627.1:c.2264G>C NP_001394556.1:p.Arg755Thr missense NM_001407628.1:c.2264G>C NP_001394557.1:p.Arg755Thr missense NM_001407629.1:c.2264G>C NP_001394558.1:p.Arg755Thr missense NM_001407630.1:c.2264G>C NP_001394559.1:p.Arg755Thr missense NM_001407631.1:c.2264G>C NP_001394560.1:p.Arg755Thr missense NM_001407632.1:c.2264G>C NP_001394561.1:p.Arg755Thr missense NM_001407633.1:c.2264G>C NP_001394562.1:p.Arg755Thr missense NM_001407634.1:c.2264G>C NP_001394563.1:p.Arg755Thr missense NM_001407635.1:c.2264G>C NP_001394564.1:p.Arg755Thr missense NM_001407636.1:c.2264G>C NP_001394565.1:p.Arg755Thr missense NM_001407637.1:c.2264G>C NP_001394566.1:p.Arg755Thr missense NM_001407638.1:c.2264G>C NP_001394567.1:p.Arg755Thr missense NM_001407639.1:c.2267G>C NP_001394568.1:p.Arg756Thr missense NM_001407640.1:c.2267G>C NP_001394569.1:p.Arg756Thr missense NM_001407641.1:c.2267G>C NP_001394570.1:p.Arg756Thr missense NM_001407642.1:c.2267G>C NP_001394571.1:p.Arg756Thr missense NM_001407644.1:c.2264G>C NP_001394573.1:p.Arg755Thr missense NM_001407645.1:c.2264G>C NP_001394574.1:p.Arg755Thr missense NM_001407646.1:c.2258G>C NP_001394575.1:p.Arg753Thr missense NM_001407647.1:c.2258G>C NP_001394576.1:p.Arg753Thr missense NM_001407648.1:c.2144G>C NP_001394577.1:p.Arg715Thr missense NM_001407649.1:c.2141G>C NP_001394578.1:p.Arg714Thr missense NM_001407652.1:c.2267G>C NP_001394581.1:p.Arg756Thr missense NM_001407653.1:c.2189G>C NP_001394582.1:p.Arg730Thr missense NM_001407654.1:c.2189G>C NP_001394583.1:p.Arg730Thr missense NM_001407655.1:c.2189G>C NP_001394584.1:p.Arg730Thr missense NM_001407656.1:c.2189G>C NP_001394585.1:p.Arg730Thr missense NM_001407657.1:c.2189G>C NP_001394586.1:p.Arg730Thr missense NM_001407658.1:c.2189G>C NP_001394587.1:p.Arg730Thr missense NM_001407659.1:c.2186G>C NP_001394588.1:p.Arg729Thr missense NM_001407660.1:c.2186G>C NP_001394589.1:p.Arg729Thr missense NM_001407661.1:c.2186G>C NP_001394590.1:p.Arg729Thr missense NM_001407662.1:c.2186G>C NP_001394591.1:p.Arg729Thr missense NM_001407663.1:c.2189G>C NP_001394592.1:p.Arg730Thr missense NM_001407664.1:c.2144G>C NP_001394593.1:p.Arg715Thr missense NM_001407665.1:c.2144G>C NP_001394594.1:p.Arg715Thr missense NM_001407666.1:c.2144G>C NP_001394595.1:p.Arg715Thr missense NM_001407667.1:c.2144G>C NP_001394596.1:p.Arg715Thr missense NM_001407668.1:c.2144G>C NP_001394597.1:p.Arg715Thr missense NM_001407669.1:c.2144G>C NP_001394598.1:p.Arg715Thr missense NM_001407670.1:c.2141G>C NP_001394599.1:p.Arg714Thr missense NM_001407671.1:c.2141G>C NP_001394600.1:p.Arg714Thr missense NM_001407672.1:c.2141G>C NP_001394601.1:p.Arg714Thr missense NM_001407673.1:c.2141G>C NP_001394602.1:p.Arg714Thr missense NM_001407674.1:c.2144G>C NP_001394603.1:p.Arg715Thr missense NM_001407675.1:c.2144G>C NP_001394604.1:p.Arg715Thr missense NM_001407676.1:c.2144G>C NP_001394605.1:p.Arg715Thr missense NM_001407677.1:c.2144G>C NP_001394606.1:p.Arg715Thr missense NM_001407678.1:c.2144G>C NP_001394607.1:p.Arg715Thr missense NM_001407679.1:c.2144G>C NP_001394608.1:p.Arg715Thr missense NM_001407680.1:c.2144G>C NP_001394609.1:p.Arg715Thr missense NM_001407681.1:c.2144G>C NP_001394610.1:p.Arg715Thr missense NM_001407682.1:c.2144G>C NP_001394611.1:p.Arg715Thr missense NM_001407683.1:c.2144G>C NP_001394612.1:p.Arg715Thr missense NM_001407684.1:c.2267G>C NP_001394613.1:p.Arg756Thr missense NM_001407685.1:c.2141G>C NP_001394614.1:p.Arg714Thr missense NM_001407686.1:c.2141G>C NP_001394615.1:p.Arg714Thr missense NM_001407687.1:c.2141G>C NP_001394616.1:p.Arg714Thr missense NM_001407688.1:c.2141G>C NP_001394617.1:p.Arg714Thr missense NM_001407689.1:c.2141G>C NP_001394618.1:p.Arg714Thr missense NM_001407690.1:c.2141G>C NP_001394619.1:p.Arg714Thr missense NM_001407691.1:c.2141G>C NP_001394620.1:p.Arg714Thr missense NM_001407692.1:c.2126G>C NP_001394621.1:p.Arg709Thr missense NM_001407694.1:c.2126G>C NP_001394623.1:p.Arg709Thr missense NM_001407695.1:c.2126G>C NP_001394624.1:p.Arg709Thr missense NM_001407696.1:c.2126G>C NP_001394625.1:p.Arg709Thr missense NM_001407697.1:c.2126G>C NP_001394626.1:p.Arg709Thr missense NM_001407698.1:c.2126G>C NP_001394627.1:p.Arg709Thr missense NM_001407724.1:c.2126G>C NP_001394653.1:p.Arg709Thr missense NM_001407725.1:c.2126G>C NP_001394654.1:p.Arg709Thr missense NM_001407726.1:c.2126G>C NP_001394655.1:p.Arg709Thr missense NM_001407727.1:c.2126G>C NP_001394656.1:p.Arg709Thr missense NM_001407728.1:c.2126G>C NP_001394657.1:p.Arg709Thr missense NM_001407729.1:c.2126G>C NP_001394658.1:p.Arg709Thr missense NM_001407730.1:c.2126G>C NP_001394659.1:p.Arg709Thr missense NM_001407731.1:c.2126G>C NP_001394660.1:p.Arg709Thr missense NM_001407732.1:c.2126G>C NP_001394661.1:p.Arg709Thr missense NM_001407733.1:c.2126G>C NP_001394662.1:p.Arg709Thr missense NM_001407734.1:c.2126G>C NP_001394663.1:p.Arg709Thr missense NM_001407735.1:c.2126G>C NP_001394664.1:p.Arg709Thr missense NM_001407736.1:c.2126G>C NP_001394665.1:p.Arg709Thr missense NM_001407737.1:c.2126G>C NP_001394666.1:p.Arg709Thr missense NM_001407738.1:c.2126G>C NP_001394667.1:p.Arg709Thr missense NM_001407739.1:c.2126G>C NP_001394668.1:p.Arg709Thr missense NM_001407740.1:c.2123G>C NP_001394669.1:p.Arg708Thr missense NM_001407741.1:c.2123G>C NP_001394670.1:p.Arg708Thr missense NM_001407742.1:c.2123G>C NP_001394671.1:p.Arg708Thr missense NM_001407743.1:c.2123G>C NP_001394672.1:p.Arg708Thr missense NM_001407744.1:c.2123G>C NP_001394673.1:p.Arg708Thr missense NM_001407745.1:c.2123G>C NP_001394674.1:p.Arg708Thr missense NM_001407746.1:c.2123G>C NP_001394675.1:p.Arg708Thr missense NM_001407747.1:c.2123G>C NP_001394676.1:p.Arg708Thr missense NM_001407748.1:c.2123G>C NP_001394677.1:p.Arg708Thr missense NM_001407749.1:c.2123G>C NP_001394678.1:p.Arg708Thr missense NM_001407750.1:c.2126G>C NP_001394679.1:p.Arg709Thr missense NM_001407751.1:c.2126G>C NP_001394680.1:p.Arg709Thr missense NM_001407752.1:c.2126G>C NP_001394681.1:p.Arg709Thr missense NM_001407838.1:c.2123G>C NP_001394767.1:p.Arg708Thr missense NM_001407839.1:c.2123G>C NP_001394768.1:p.Arg708Thr missense NM_001407841.1:c.2123G>C NP_001394770.1:p.Arg708Thr missense NM_001407842.1:c.2123G>C NP_001394771.1:p.Arg708Thr missense NM_001407843.1:c.2123G>C NP_001394772.1:p.Arg708Thr missense NM_001407844.1:c.2123G>C NP_001394773.1:p.Arg708Thr missense NM_001407845.1:c.2123G>C NP_001394774.1:p.Arg708Thr missense NM_001407846.1:c.2123G>C NP_001394775.1:p.Arg708Thr missense NM_001407847.1:c.2123G>C NP_001394776.1:p.Arg708Thr missense NM_001407848.1:c.2123G>C NP_001394777.1:p.Arg708Thr missense NM_001407849.1:c.2123G>C NP_001394778.1:p.Arg708Thr missense NM_001407850.1:c.2126G>C NP_001394779.1:p.Arg709Thr missense NM_001407851.1:c.2126G>C NP_001394780.1:p.Arg709Thr missense NM_001407852.1:c.2126G>C NP_001394781.1:p.Arg709Thr missense NM_001407853.1:c.2054G>C NP_001394782.1:p.Arg685Thr missense NM_001407854.1:c.2267G>C NP_001394783.1:p.Arg756Thr missense NM_001407858.1:c.2267G>C NP_001394787.1:p.Arg756Thr missense NM_001407859.1:c.2267G>C NP_001394788.1:p.Arg756Thr missense NM_001407860.1:c.2264G>C NP_001394789.1:p.Arg755Thr missense NM_001407861.1:c.2264G>C NP_001394790.1:p.Arg755Thr missense NM_001407862.1:c.2066G>C NP_001394791.1:p.Arg689Thr missense NM_001407863.1:c.2144G>C NP_001394792.1:p.Arg715Thr missense NM_001407874.1:c.2063G>C NP_001394803.1:p.Arg688Thr missense NM_001407875.1:c.2063G>C NP_001394804.1:p.Arg688Thr missense NM_001407879.1:c.2057G>C NP_001394808.1:p.Arg686Thr missense NM_001407881.1:c.2057G>C NP_001394810.1:p.Arg686Thr missense NM_001407882.1:c.2057G>C NP_001394811.1:p.Arg686Thr missense NM_001407884.1:c.2057G>C NP_001394813.1:p.Arg686Thr missense NM_001407885.1:c.2057G>C NP_001394814.1:p.Arg686Thr missense NM_001407886.1:c.2057G>C NP_001394815.1:p.Arg686Thr missense NM_001407887.1:c.2057G>C NP_001394816.1:p.Arg686Thr missense NM_001407889.1:c.2057G>C NP_001394818.1:p.Arg686Thr missense NM_001407894.1:c.2054G>C NP_001394823.1:p.Arg685Thr missense NM_001407895.1:c.2054G>C NP_001394824.1:p.Arg685Thr missense NM_001407896.1:c.2054G>C NP_001394825.1:p.Arg685Thr missense NM_001407897.1:c.2054G>C NP_001394826.1:p.Arg685Thr missense NM_001407898.1:c.2054G>C NP_001394827.1:p.Arg685Thr missense NM_001407899.1:c.2054G>C NP_001394828.1:p.Arg685Thr missense NM_001407900.1:c.2057G>C NP_001394829.1:p.Arg686Thr missense NM_001407902.1:c.2057G>C NP_001394831.1:p.Arg686Thr missense NM_001407904.1:c.2057G>C NP_001394833.1:p.Arg686Thr missense NM_001407906.1:c.2057G>C NP_001394835.1:p.Arg686Thr missense NM_001407907.1:c.2057G>C NP_001394836.1:p.Arg686Thr missense NM_001407908.1:c.2057G>C NP_001394837.1:p.Arg686Thr missense NM_001407909.1:c.2057G>C NP_001394838.1:p.Arg686Thr missense NM_001407910.1:c.2057G>C NP_001394839.1:p.Arg686Thr missense NM_001407915.1:c.2054G>C NP_001394844.1:p.Arg685Thr missense NM_001407916.1:c.2054G>C NP_001394845.1:p.Arg685Thr missense NM_001407917.1:c.2054G>C NP_001394846.1:p.Arg685Thr missense NM_001407918.1:c.2054G>C NP_001394847.1:p.Arg685Thr missense NM_001407919.1:c.2144G>C NP_001394848.1:p.Arg715Thr missense NM_001407920.1:c.2003G>C NP_001394849.1:p.Arg668Thr missense NM_001407921.1:c.2003G>C NP_001394850.1:p.Arg668Thr missense NM_001407922.1:c.2003G>C NP_001394851.1:p.Arg668Thr missense NM_001407923.1:c.2003G>C NP_001394852.1:p.Arg668Thr missense NM_001407924.1:c.2003G>C NP_001394853.1:p.Arg668Thr missense NM_001407925.1:c.2003G>C NP_001394854.1:p.Arg668Thr missense NM_001407926.1:c.2003G>C NP_001394855.1:p.Arg668Thr missense NM_001407927.1:c.2003G>C NP_001394856.1:p.Arg668Thr missense NM_001407928.1:c.2003G>C NP_001394857.1:p.Arg668Thr missense NM_001407929.1:c.2003G>C NP_001394858.1:p.Arg668Thr missense NM_001407930.1:c.2000G>C NP_001394859.1:p.Arg667Thr missense NM_001407931.1:c.2000G>C NP_001394860.1:p.Arg667Thr missense NM_001407932.1:c.2000G>C NP_001394861.1:p.Arg667Thr missense NM_001407933.1:c.2003G>C NP_001394862.1:p.Arg668Thr missense NM_001407934.1:c.2000G>C NP_001394863.1:p.Arg667Thr missense NM_001407935.1:c.2003G>C NP_001394864.1:p.Arg668Thr missense NM_001407936.1:c.2000G>C NP_001394865.1:p.Arg667Thr missense NM_001407937.1:c.2144G>C NP_001394866.1:p.Arg715Thr missense NM_001407938.1:c.2144G>C NP_001394867.1:p.Arg715Thr missense NM_001407939.1:c.2144G>C NP_001394868.1:p.Arg715Thr missense NM_001407940.1:c.2141G>C NP_001394869.1:p.Arg714Thr missense NM_001407941.1:c.2141G>C NP_001394870.1:p.Arg714Thr missense NM_001407942.1:c.2126G>C NP_001394871.1:p.Arg709Thr missense NM_001407943.1:c.2123G>C NP_001394872.1:p.Arg708Thr missense NM_001407944.1:c.2126G>C NP_001394873.1:p.Arg709Thr missense NM_001407945.1:c.2126G>C NP_001394874.1:p.Arg709Thr missense NM_001407946.1:c.1934G>C NP_001394875.1:p.Arg645Thr missense NM_001407947.1:c.1934G>C NP_001394876.1:p.Arg645Thr missense NM_001407948.1:c.1934G>C NP_001394877.1:p.Arg645Thr missense NM_001407949.1:c.1934G>C NP_001394878.1:p.Arg645Thr missense NM_001407950.1:c.1934G>C NP_001394879.1:p.Arg645Thr missense NM_001407951.1:c.1934G>C NP_001394880.1:p.Arg645Thr missense NM_001407952.1:c.1934G>C NP_001394881.1:p.Arg645Thr missense NM_001407953.1:c.1934G>C NP_001394882.1:p.Arg645Thr missense NM_001407954.1:c.1931G>C NP_001394883.1:p.Arg644Thr missense NM_001407955.1:c.1931G>C NP_001394884.1:p.Arg644Thr missense NM_001407956.1:c.1931G>C NP_001394885.1:p.Arg644Thr missense NM_001407957.1:c.1934G>C NP_001394886.1:p.Arg645Thr missense NM_001407958.1:c.1931G>C NP_001394887.1:p.Arg644Thr missense NM_001407959.1:c.1886G>C NP_001394888.1:p.Arg629Thr missense NM_001407960.1:c.1886G>C NP_001394889.1:p.Arg629Thr missense NM_001407962.1:c.1883G>C NP_001394891.1:p.Arg628Thr missense NM_001407963.1:c.1886G>C NP_001394892.1:p.Arg629Thr missense NM_001407964.1:c.2123G>C NP_001394893.1:p.Arg708Thr missense NM_001407965.1:c.1763G>C NP_001394894.1:p.Arg588Thr missense NM_001407966.1:c.1379G>C NP_001394895.1:p.Arg460Thr missense NM_001407967.1:c.1379G>C NP_001394896.1:p.Arg460Thr missense NM_001407968.1:c.788-1125G>C intron variant NM_001407969.1:c.788-1125G>C intron variant NM_001407970.1:c.787+1480G>C intron variant NM_001407971.1:c.787+1480G>C intron variant NM_001407972.1:c.784+1480G>C intron variant NM_001407973.1:c.787+1480G>C intron variant NM_001407974.1:c.787+1480G>C intron variant NM_001407975.1:c.787+1480G>C intron variant NM_001407976.1:c.787+1480G>C intron variant NM_001407977.1:c.787+1480G>C intron variant NM_001407978.1:c.787+1480G>C intron variant NM_001407979.1:c.787+1480G>C intron variant NM_001407980.1:c.787+1480G>C intron variant NM_001407981.1:c.787+1480G>C intron variant NM_001407982.1:c.787+1480G>C intron variant NM_001407983.1:c.787+1480G>C intron variant NM_001407984.1:c.784+1480G>C intron variant NM_001407985.1:c.784+1480G>C intron variant NM_001407986.1:c.784+1480G>C intron variant NM_001407990.1:c.787+1480G>C intron variant NM_001407991.1:c.784+1480G>C intron variant NM_001407992.1:c.784+1480G>C intron variant NM_001407993.1:c.787+1480G>C intron variant NM_001408392.1:c.784+1480G>C intron variant NM_001408396.1:c.784+1480G>C intron variant NM_001408397.1:c.784+1480G>C intron variant NM_001408398.1:c.784+1480G>C intron variant NM_001408399.1:c.784+1480G>C intron variant NM_001408400.1:c.784+1480G>C intron variant NM_001408401.1:c.784+1480G>C intron variant NM_001408402.1:c.784+1480G>C intron variant NM_001408403.1:c.787+1480G>C intron variant NM_001408404.1:c.787+1480G>C intron variant NM_001408406.1:c.790+1477G>C intron variant NM_001408407.1:c.784+1480G>C intron variant NM_001408408.1:c.778+1480G>C intron variant NM_001408409.1:c.709+1480G>C intron variant NM_001408410.1:c.646+1480G>C intron variant NM_001408411.1:c.709+1480G>C intron variant NM_001408412.1:c.709+1480G>C intron variant NM_001408413.1:c.706+1480G>C intron variant NM_001408414.1:c.709+1480G>C intron variant NM_001408415.1:c.709+1480G>C intron variant NM_001408416.1:c.706+1480G>C intron variant NM_001408418.1:c.671-2232G>C intron variant NM_001408419.1:c.671-2232G>C intron variant NM_001408420.1:c.671-2232G>C intron variant NM_001408421.1:c.668-2232G>C intron variant NM_001408422.1:c.671-2232G>C intron variant NM_001408423.1:c.671-2232G>C intron variant NM_001408424.1:c.668-2232G>C intron variant NM_001408425.1:c.664+1480G>C intron variant NM_001408426.1:c.664+1480G>C intron variant NM_001408427.1:c.664+1480G>C intron variant NM_001408428.1:c.664+1480G>C intron variant NM_001408429.1:c.664+1480G>C intron variant NM_001408430.1:c.664+1480G>C intron variant NM_001408431.1:c.668-2232G>C intron variant NM_001408432.1:c.661+1480G>C intron variant NM_001408433.1:c.661+1480G>C intron variant NM_001408434.1:c.661+1480G>C intron variant NM_001408435.1:c.661+1480G>C intron variant NM_001408436.1:c.664+1480G>C intron variant NM_001408437.1:c.664+1480G>C intron variant NM_001408438.1:c.664+1480G>C intron variant NM_001408439.1:c.664+1480G>C intron variant NM_001408440.1:c.664+1480G>C intron variant NM_001408441.1:c.664+1480G>C intron variant NM_001408442.1:c.664+1480G>C intron variant NM_001408443.1:c.664+1480G>C intron variant NM_001408444.1:c.664+1480G>C intron variant NM_001408445.1:c.661+1480G>C intron variant NM_001408446.1:c.661+1480G>C intron variant NM_001408447.1:c.661+1480G>C intron variant NM_001408448.1:c.661+1480G>C intron variant NM_001408450.1:c.661+1480G>C intron variant NM_001408451.1:c.652+1480G>C intron variant NM_001408452.1:c.646+1480G>C intron variant NM_001408453.1:c.646+1480G>C intron variant NM_001408454.1:c.646+1480G>C intron variant NM_001408455.1:c.646+1480G>C intron variant NM_001408456.1:c.646+1480G>C intron variant NM_001408457.1:c.646+1480G>C intron variant NM_001408458.1:c.646+1480G>C intron variant NM_001408459.1:c.646+1480G>C intron variant NM_001408460.1:c.646+1480G>C intron variant NM_001408461.1:c.646+1480G>C intron variant NM_001408462.1:c.643+1480G>C intron variant NM_001408463.1:c.643+1480G>C intron variant NM_001408464.1:c.643+1480G>C intron variant NM_001408465.1:c.643+1480G>C intron variant NM_001408466.1:c.646+1480G>C intron variant NM_001408467.1:c.646+1480G>C intron variant NM_001408468.1:c.643+1480G>C intron variant NM_001408469.1:c.646+1480G>C intron variant NM_001408470.1:c.643+1480G>C intron variant NM_001408472.1:c.787+1480G>C intron variant NM_001408473.1:c.784+1480G>C intron variant NM_001408474.1:c.586+1480G>C intron variant NM_001408475.1:c.583+1480G>C intron variant NM_001408476.1:c.586+1480G>C intron variant NM_001408478.1:c.577+1480G>C intron variant NM_001408479.1:c.577+1480G>C intron variant NM_001408480.1:c.577+1480G>C intron variant NM_001408481.1:c.577+1480G>C intron variant NM_001408482.1:c.577+1480G>C intron variant NM_001408483.1:c.577+1480G>C intron variant NM_001408484.1:c.577+1480G>C intron variant NM_001408485.1:c.577+1480G>C intron variant NM_001408489.1:c.577+1480G>C intron variant NM_001408490.1:c.574+1480G>C intron variant NM_001408491.1:c.574+1480G>C intron variant NM_001408492.1:c.577+1480G>C intron variant NM_001408493.1:c.574+1480G>C intron variant NM_001408494.1:c.548-2232G>C intron variant NM_001408495.1:c.545-2232G>C intron variant NM_001408496.1:c.523+1480G>C intron variant NM_001408497.1:c.523+1480G>C intron variant NM_001408498.1:c.523+1480G>C intron variant NM_001408499.1:c.523+1480G>C intron variant NM_001408500.1:c.523+1480G>C intron variant NM_001408501.1:c.523+1480G>C intron variant NM_001408502.1:c.454+1480G>C intron variant NM_001408503.1:c.520+1480G>C intron variant NM_001408504.1:c.520+1480G>C intron variant NM_001408505.1:c.520+1480G>C intron variant NM_001408506.1:c.461-2232G>C intron variant NM_001408507.1:c.461-2232G>C intron variant NM_001408508.1:c.451+1480G>C intron variant NM_001408509.1:c.451+1480G>C intron variant NM_001408510.1:c.406+1480G>C intron variant NM_001408511.1:c.404-2232G>C intron variant NM_001408512.1:c.283+1480G>C intron variant NM_001408513.1:c.577+1480G>C intron variant NM_001408514.1:c.577+1480G>C intron variant NM_007297.4:c.2126G>C NP_009228.2:p.Arg709Thr missense NM_007298.4:c.787+1480G>C intron variant NM_007299.4:c.787+1480G>C intron variant NM_007300.4:c.2267G>C NP_009231.2:p.Arg756Thr missense NR_027676.1:n.2403G>C NC_000017.11:g.43093264C>G NC_000017.10:g.41245281C>G NG_005905.2:g.124720G>C LRG_292:g.124720G>C LRG_292t1:c.2267G>C LRG_292p1:p.Arg756Thr - Protein change
- R709T, R756T, R588T, R645T, R667T, R686T, R689T, R708T, R714T, R628T, R629T, R715T, R729T, R753T, R460T, R644T, R668T, R730T, R755T, R685T, R688T
- Other names
- -
- Canonical SPDI
- NC_000017.11:43093263:C: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 |
13044 | 14850 | |
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
|
Nov 13, 2019 | RCV001240986.8 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 23, 2023 | RCV003158602.3 |
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. |
|
|---|---|---|---|---|---|
|
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: SCV003847801.1
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
(Nov 13, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001413975.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 756 of the BRCA1 protein (p.Arg756Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine. (less)
|
Comment:
Comment:
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 756 of the BRCA1 protein (p.Arg756Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine.
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:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 756 of the BRCA1 protein (p.Arg756Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine.
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 |
Text-mined citations for rs975724885 ...
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 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.