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.1870G>A (p.Glu624Lys)
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.
(3)
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)
3
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.1870G>A (p.Glu624Lys)
Variation ID: 54374 Accession: VCV000054374.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093661 (GRCh38) [ NCBI UCSC ] 17: 41245678 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Feb 14, 2024 Mar 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.1870G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu624Lys missense NM_001407571.1:c.1657G>A NP_001394500.1:p.Glu553Lys missense NM_001407581.1:c.1870G>A NP_001394510.1:p.Glu624Lys missense NM_001407582.1:c.1870G>A NP_001394511.1:p.Glu624Lys missense NM_001407583.1:c.1870G>A NP_001394512.1:p.Glu624Lys missense NM_001407585.1:c.1870G>A NP_001394514.1:p.Glu624Lys missense NM_001407587.1:c.1867G>A NP_001394516.1:p.Glu623Lys missense NM_001407590.1:c.1867G>A NP_001394519.1:p.Glu623Lys missense NM_001407591.1:c.1867G>A NP_001394520.1:p.Glu623Lys missense NM_001407593.1:c.1870G>A NP_001394522.1:p.Glu624Lys missense NM_001407594.1:c.1870G>A NP_001394523.1:p.Glu624Lys missense NM_001407596.1:c.1870G>A NP_001394525.1:p.Glu624Lys missense NM_001407597.1:c.1870G>A NP_001394526.1:p.Glu624Lys missense NM_001407598.1:c.1870G>A NP_001394527.1:p.Glu624Lys missense NM_001407602.1:c.1870G>A NP_001394531.1:p.Glu624Lys missense NM_001407603.1:c.1870G>A NP_001394532.1:p.Glu624Lys missense NM_001407605.1:c.1870G>A NP_001394534.1:p.Glu624Lys missense NM_001407610.1:c.1867G>A NP_001394539.1:p.Glu623Lys missense NM_001407611.1:c.1867G>A NP_001394540.1:p.Glu623Lys missense NM_001407612.1:c.1867G>A NP_001394541.1:p.Glu623Lys missense NM_001407613.1:c.1867G>A NP_001394542.1:p.Glu623Lys missense NM_001407614.1:c.1867G>A NP_001394543.1:p.Glu623Lys missense NM_001407615.1:c.1867G>A NP_001394544.1:p.Glu623Lys missense NM_001407616.1:c.1870G>A NP_001394545.1:p.Glu624Lys missense NM_001407617.1:c.1870G>A NP_001394546.1:p.Glu624Lys missense NM_001407618.1:c.1870G>A NP_001394547.1:p.Glu624Lys missense NM_001407619.1:c.1870G>A NP_001394548.1:p.Glu624Lys missense NM_001407620.1:c.1870G>A NP_001394549.1:p.Glu624Lys missense NM_001407621.1:c.1870G>A NP_001394550.1:p.Glu624Lys missense NM_001407622.1:c.1870G>A NP_001394551.1:p.Glu624Lys missense NM_001407623.1:c.1870G>A NP_001394552.1:p.Glu624Lys missense NM_001407624.1:c.1870G>A NP_001394553.1:p.Glu624Lys missense NM_001407625.1:c.1870G>A NP_001394554.1:p.Glu624Lys missense NM_001407626.1:c.1870G>A NP_001394555.1:p.Glu624Lys missense NM_001407627.1:c.1867G>A NP_001394556.1:p.Glu623Lys missense NM_001407628.1:c.1867G>A NP_001394557.1:p.Glu623Lys missense NM_001407629.1:c.1867G>A NP_001394558.1:p.Glu623Lys missense NM_001407630.1:c.1867G>A NP_001394559.1:p.Glu623Lys missense NM_001407631.1:c.1867G>A NP_001394560.1:p.Glu623Lys missense NM_001407632.1:c.1867G>A NP_001394561.1:p.Glu623Lys missense NM_001407633.1:c.1867G>A NP_001394562.1:p.Glu623Lys missense NM_001407634.1:c.1867G>A NP_001394563.1:p.Glu623Lys missense NM_001407635.1:c.1867G>A NP_001394564.1:p.Glu623Lys missense NM_001407636.1:c.1867G>A NP_001394565.1:p.Glu623Lys missense NM_001407637.1:c.1867G>A NP_001394566.1:p.Glu623Lys missense NM_001407638.1:c.1867G>A NP_001394567.1:p.Glu623Lys missense NM_001407639.1:c.1870G>A NP_001394568.1:p.Glu624Lys missense NM_001407640.1:c.1870G>A NP_001394569.1:p.Glu624Lys missense NM_001407641.1:c.1870G>A NP_001394570.1:p.Glu624Lys missense NM_001407642.1:c.1870G>A NP_001394571.1:p.Glu624Lys missense NM_001407644.1:c.1867G>A NP_001394573.1:p.Glu623Lys missense NM_001407645.1:c.1867G>A NP_001394574.1:p.Glu623Lys missense NM_001407646.1:c.1861G>A NP_001394575.1:p.Glu621Lys missense NM_001407647.1:c.1861G>A NP_001394576.1:p.Glu621Lys missense NM_001407648.1:c.1747G>A NP_001394577.1:p.Glu583Lys missense NM_001407649.1:c.1744G>A NP_001394578.1:p.Glu582Lys missense NM_001407652.1:c.1870G>A NP_001394581.1:p.Glu624Lys missense NM_001407653.1:c.1792G>A NP_001394582.1:p.Glu598Lys missense NM_001407654.1:c.1792G>A NP_001394583.1:p.Glu598Lys missense NM_001407655.1:c.1792G>A NP_001394584.1:p.Glu598Lys missense NM_001407656.1:c.1792G>A NP_001394585.1:p.Glu598Lys missense NM_001407657.1:c.1792G>A NP_001394586.1:p.Glu598Lys missense NM_001407658.1:c.1792G>A NP_001394587.1:p.Glu598Lys missense NM_001407659.1:c.1789G>A NP_001394588.1:p.Glu597Lys missense NM_001407660.1:c.1789G>A NP_001394589.1:p.Glu597Lys missense NM_001407661.1:c.1789G>A NP_001394590.1:p.Glu597Lys missense NM_001407662.1:c.1789G>A NP_001394591.1:p.Glu597Lys missense NM_001407663.1:c.1792G>A NP_001394592.1:p.Glu598Lys missense NM_001407664.1:c.1747G>A NP_001394593.1:p.Glu583Lys missense NM_001407665.1:c.1747G>A NP_001394594.1:p.Glu583Lys missense NM_001407666.1:c.1747G>A NP_001394595.1:p.Glu583Lys missense NM_001407667.1:c.1747G>A NP_001394596.1:p.Glu583Lys missense NM_001407668.1:c.1747G>A NP_001394597.1:p.Glu583Lys missense NM_001407669.1:c.1747G>A NP_001394598.1:p.Glu583Lys missense NM_001407670.1:c.1744G>A NP_001394599.1:p.Glu582Lys missense NM_001407671.1:c.1744G>A NP_001394600.1:p.Glu582Lys missense NM_001407672.1:c.1744G>A NP_001394601.1:p.Glu582Lys missense NM_001407673.1:c.1744G>A NP_001394602.1:p.Glu582Lys missense NM_001407674.1:c.1747G>A NP_001394603.1:p.Glu583Lys missense NM_001407675.1:c.1747G>A NP_001394604.1:p.Glu583Lys missense NM_001407676.1:c.1747G>A NP_001394605.1:p.Glu583Lys missense NM_001407677.1:c.1747G>A NP_001394606.1:p.Glu583Lys missense NM_001407678.1:c.1747G>A NP_001394607.1:p.Glu583Lys missense NM_001407679.1:c.1747G>A NP_001394608.1:p.Glu583Lys missense NM_001407680.1:c.1747G>A NP_001394609.1:p.Glu583Lys missense NM_001407681.1:c.1747G>A NP_001394610.1:p.Glu583Lys missense NM_001407682.1:c.1747G>A NP_001394611.1:p.Glu583Lys missense NM_001407683.1:c.1747G>A NP_001394612.1:p.Glu583Lys missense NM_001407684.1:c.1870G>A NP_001394613.1:p.Glu624Lys missense NM_001407685.1:c.1744G>A NP_001394614.1:p.Glu582Lys missense NM_001407686.1:c.1744G>A NP_001394615.1:p.Glu582Lys missense NM_001407687.1:c.1744G>A NP_001394616.1:p.Glu582Lys missense NM_001407688.1:c.1744G>A NP_001394617.1:p.Glu582Lys missense NM_001407689.1:c.1744G>A NP_001394618.1:p.Glu582Lys missense NM_001407690.1:c.1744G>A NP_001394619.1:p.Glu582Lys missense NM_001407691.1:c.1744G>A NP_001394620.1:p.Glu582Lys missense NM_001407692.1:c.1729G>A NP_001394621.1:p.Glu577Lys missense NM_001407694.1:c.1729G>A NP_001394623.1:p.Glu577Lys missense NM_001407695.1:c.1729G>A NP_001394624.1:p.Glu577Lys missense NM_001407696.1:c.1729G>A NP_001394625.1:p.Glu577Lys missense NM_001407697.1:c.1729G>A NP_001394626.1:p.Glu577Lys missense NM_001407698.1:c.1729G>A NP_001394627.1:p.Glu577Lys missense NM_001407724.1:c.1729G>A NP_001394653.1:p.Glu577Lys missense NM_001407725.1:c.1729G>A NP_001394654.1:p.Glu577Lys missense NM_001407726.1:c.1729G>A NP_001394655.1:p.Glu577Lys missense NM_001407727.1:c.1729G>A NP_001394656.1:p.Glu577Lys missense NM_001407728.1:c.1729G>A NP_001394657.1:p.Glu577Lys missense NM_001407729.1:c.1729G>A NP_001394658.1:p.Glu577Lys missense NM_001407730.1:c.1729G>A NP_001394659.1:p.Glu577Lys missense NM_001407731.1:c.1729G>A NP_001394660.1:p.Glu577Lys missense NM_001407732.1:c.1729G>A NP_001394661.1:p.Glu577Lys missense NM_001407733.1:c.1729G>A NP_001394662.1:p.Glu577Lys missense NM_001407734.1:c.1729G>A NP_001394663.1:p.Glu577Lys missense NM_001407735.1:c.1729G>A NP_001394664.1:p.Glu577Lys missense NM_001407736.1:c.1729G>A NP_001394665.1:p.Glu577Lys missense NM_001407737.1:c.1729G>A NP_001394666.1:p.Glu577Lys missense NM_001407738.1:c.1729G>A NP_001394667.1:p.Glu577Lys missense NM_001407739.1:c.1729G>A NP_001394668.1:p.Glu577Lys missense NM_001407740.1:c.1726G>A NP_001394669.1:p.Glu576Lys missense NM_001407741.1:c.1726G>A NP_001394670.1:p.Glu576Lys missense NM_001407742.1:c.1726G>A NP_001394671.1:p.Glu576Lys missense NM_001407743.1:c.1726G>A NP_001394672.1:p.Glu576Lys missense NM_001407744.1:c.1726G>A NP_001394673.1:p.Glu576Lys missense NM_001407745.1:c.1726G>A NP_001394674.1:p.Glu576Lys missense NM_001407746.1:c.1726G>A NP_001394675.1:p.Glu576Lys missense NM_001407747.1:c.1726G>A NP_001394676.1:p.Glu576Lys missense NM_001407748.1:c.1726G>A NP_001394677.1:p.Glu576Lys missense NM_001407749.1:c.1726G>A NP_001394678.1:p.Glu576Lys missense NM_001407750.1:c.1729G>A NP_001394679.1:p.Glu577Lys missense NM_001407751.1:c.1729G>A NP_001394680.1:p.Glu577Lys missense NM_001407752.1:c.1729G>A NP_001394681.1:p.Glu577Lys missense NM_001407838.1:c.1726G>A NP_001394767.1:p.Glu576Lys missense NM_001407839.1:c.1726G>A NP_001394768.1:p.Glu576Lys missense NM_001407841.1:c.1726G>A NP_001394770.1:p.Glu576Lys missense NM_001407842.1:c.1726G>A NP_001394771.1:p.Glu576Lys missense NM_001407843.1:c.1726G>A NP_001394772.1:p.Glu576Lys missense NM_001407844.1:c.1726G>A NP_001394773.1:p.Glu576Lys missense NM_001407845.1:c.1726G>A NP_001394774.1:p.Glu576Lys missense NM_001407846.1:c.1726G>A NP_001394775.1:p.Glu576Lys missense NM_001407847.1:c.1726G>A NP_001394776.1:p.Glu576Lys missense NM_001407848.1:c.1726G>A NP_001394777.1:p.Glu576Lys missense NM_001407849.1:c.1726G>A NP_001394778.1:p.Glu576Lys missense NM_001407850.1:c.1729G>A NP_001394779.1:p.Glu577Lys missense NM_001407851.1:c.1729G>A NP_001394780.1:p.Glu577Lys missense NM_001407852.1:c.1729G>A NP_001394781.1:p.Glu577Lys missense NM_001407853.1:c.1657G>A NP_001394782.1:p.Glu553Lys missense NM_001407854.1:c.1870G>A NP_001394783.1:p.Glu624Lys missense NM_001407858.1:c.1870G>A NP_001394787.1:p.Glu624Lys missense NM_001407859.1:c.1870G>A NP_001394788.1:p.Glu624Lys missense NM_001407860.1:c.1867G>A NP_001394789.1:p.Glu623Lys missense NM_001407861.1:c.1867G>A NP_001394790.1:p.Glu623Lys missense NM_001407862.1:c.1669G>A NP_001394791.1:p.Glu557Lys missense NM_001407863.1:c.1747G>A NP_001394792.1:p.Glu583Lys missense NM_001407874.1:c.1666G>A NP_001394803.1:p.Glu556Lys missense NM_001407875.1:c.1666G>A NP_001394804.1:p.Glu556Lys missense NM_001407879.1:c.1660G>A NP_001394808.1:p.Glu554Lys missense NM_001407881.1:c.1660G>A NP_001394810.1:p.Glu554Lys missense NM_001407882.1:c.1660G>A NP_001394811.1:p.Glu554Lys missense NM_001407884.1:c.1660G>A NP_001394813.1:p.Glu554Lys missense NM_001407885.1:c.1660G>A NP_001394814.1:p.Glu554Lys missense NM_001407886.1:c.1660G>A NP_001394815.1:p.Glu554Lys missense NM_001407887.1:c.1660G>A NP_001394816.1:p.Glu554Lys missense NM_001407889.1:c.1660G>A NP_001394818.1:p.Glu554Lys missense NM_001407894.1:c.1657G>A NP_001394823.1:p.Glu553Lys missense NM_001407895.1:c.1657G>A NP_001394824.1:p.Glu553Lys missense NM_001407896.1:c.1657G>A NP_001394825.1:p.Glu553Lys missense NM_001407897.1:c.1657G>A NP_001394826.1:p.Glu553Lys missense NM_001407898.1:c.1657G>A NP_001394827.1:p.Glu553Lys missense NM_001407899.1:c.1657G>A NP_001394828.1:p.Glu553Lys missense NM_001407900.1:c.1660G>A NP_001394829.1:p.Glu554Lys missense NM_001407902.1:c.1660G>A NP_001394831.1:p.Glu554Lys missense NM_001407904.1:c.1660G>A NP_001394833.1:p.Glu554Lys missense NM_001407906.1:c.1660G>A NP_001394835.1:p.Glu554Lys missense NM_001407907.1:c.1660G>A NP_001394836.1:p.Glu554Lys missense NM_001407908.1:c.1660G>A NP_001394837.1:p.Glu554Lys missense NM_001407909.1:c.1660G>A NP_001394838.1:p.Glu554Lys missense NM_001407910.1:c.1660G>A NP_001394839.1:p.Glu554Lys missense NM_001407915.1:c.1657G>A NP_001394844.1:p.Glu553Lys missense NM_001407916.1:c.1657G>A NP_001394845.1:p.Glu553Lys missense NM_001407917.1:c.1657G>A NP_001394846.1:p.Glu553Lys missense NM_001407918.1:c.1657G>A NP_001394847.1:p.Glu553Lys missense NM_001407919.1:c.1747G>A NP_001394848.1:p.Glu583Lys missense NM_001407920.1:c.1606G>A NP_001394849.1:p.Glu536Lys missense NM_001407921.1:c.1606G>A NP_001394850.1:p.Glu536Lys missense NM_001407922.1:c.1606G>A NP_001394851.1:p.Glu536Lys missense NM_001407923.1:c.1606G>A NP_001394852.1:p.Glu536Lys missense NM_001407924.1:c.1606G>A NP_001394853.1:p.Glu536Lys missense NM_001407925.1:c.1606G>A NP_001394854.1:p.Glu536Lys missense NM_001407926.1:c.1606G>A NP_001394855.1:p.Glu536Lys missense NM_001407927.1:c.1606G>A NP_001394856.1:p.Glu536Lys missense NM_001407928.1:c.1606G>A NP_001394857.1:p.Glu536Lys missense NM_001407929.1:c.1606G>A NP_001394858.1:p.Glu536Lys missense NM_001407930.1:c.1603G>A NP_001394859.1:p.Glu535Lys missense NM_001407931.1:c.1603G>A NP_001394860.1:p.Glu535Lys missense NM_001407932.1:c.1603G>A NP_001394861.1:p.Glu535Lys missense NM_001407933.1:c.1606G>A NP_001394862.1:p.Glu536Lys missense NM_001407934.1:c.1603G>A NP_001394863.1:p.Glu535Lys missense NM_001407935.1:c.1606G>A NP_001394864.1:p.Glu536Lys missense NM_001407936.1:c.1603G>A NP_001394865.1:p.Glu535Lys missense NM_001407937.1:c.1747G>A NP_001394866.1:p.Glu583Lys missense NM_001407938.1:c.1747G>A NP_001394867.1:p.Glu583Lys missense NM_001407939.1:c.1747G>A NP_001394868.1:p.Glu583Lys missense NM_001407940.1:c.1744G>A NP_001394869.1:p.Glu582Lys missense NM_001407941.1:c.1744G>A NP_001394870.1:p.Glu582Lys missense NM_001407942.1:c.1729G>A NP_001394871.1:p.Glu577Lys missense NM_001407943.1:c.1726G>A NP_001394872.1:p.Glu576Lys missense NM_001407944.1:c.1729G>A NP_001394873.1:p.Glu577Lys missense NM_001407945.1:c.1729G>A NP_001394874.1:p.Glu577Lys missense NM_001407946.1:c.1537G>A NP_001394875.1:p.Glu513Lys missense NM_001407947.1:c.1537G>A NP_001394876.1:p.Glu513Lys missense NM_001407948.1:c.1537G>A NP_001394877.1:p.Glu513Lys missense NM_001407949.1:c.1537G>A NP_001394878.1:p.Glu513Lys missense NM_001407950.1:c.1537G>A NP_001394879.1:p.Glu513Lys missense NM_001407951.1:c.1537G>A NP_001394880.1:p.Glu513Lys missense NM_001407952.1:c.1537G>A NP_001394881.1:p.Glu513Lys missense NM_001407953.1:c.1537G>A NP_001394882.1:p.Glu513Lys missense NM_001407954.1:c.1534G>A NP_001394883.1:p.Glu512Lys missense NM_001407955.1:c.1534G>A NP_001394884.1:p.Glu512Lys missense NM_001407956.1:c.1534G>A NP_001394885.1:p.Glu512Lys missense NM_001407957.1:c.1537G>A NP_001394886.1:p.Glu513Lys missense NM_001407958.1:c.1534G>A NP_001394887.1:p.Glu512Lys missense NM_001407959.1:c.1489G>A NP_001394888.1:p.Glu497Lys missense NM_001407960.1:c.1489G>A NP_001394889.1:p.Glu497Lys missense NM_001407962.1:c.1486G>A NP_001394891.1:p.Glu496Lys missense NM_001407963.1:c.1489G>A NP_001394892.1:p.Glu497Lys missense NM_001407964.1:c.1726G>A NP_001394893.1:p.Glu576Lys missense NM_001407965.1:c.1366G>A NP_001394894.1:p.Glu456Lys missense NM_001407966.1:c.982G>A NP_001394895.1:p.Glu328Lys missense NM_001407967.1:c.982G>A NP_001394896.1:p.Glu328Lys missense NM_001407968.1:c.787+1083G>A intron variant NM_001407969.1:c.787+1083G>A intron variant NM_001407970.1:c.787+1083G>A intron variant NM_001407971.1:c.787+1083G>A intron variant NM_001407972.1:c.784+1083G>A intron variant NM_001407973.1:c.787+1083G>A intron variant NM_001407974.1:c.787+1083G>A intron variant NM_001407975.1:c.787+1083G>A intron variant NM_001407976.1:c.787+1083G>A intron variant NM_001407977.1:c.787+1083G>A intron variant NM_001407978.1:c.787+1083G>A intron variant NM_001407979.1:c.787+1083G>A intron variant NM_001407980.1:c.787+1083G>A intron variant NM_001407981.1:c.787+1083G>A intron variant NM_001407982.1:c.787+1083G>A intron variant NM_001407983.1:c.787+1083G>A intron variant NM_001407984.1:c.784+1083G>A intron variant NM_001407985.1:c.784+1083G>A intron variant NM_001407986.1:c.784+1083G>A intron variant NM_001407990.1:c.787+1083G>A intron variant NM_001407991.1:c.784+1083G>A intron variant NM_001407992.1:c.784+1083G>A intron variant NM_001407993.1:c.787+1083G>A intron variant NM_001408392.1:c.784+1083G>A intron variant NM_001408396.1:c.784+1083G>A intron variant NM_001408397.1:c.784+1083G>A intron variant NM_001408398.1:c.784+1083G>A intron variant NM_001408399.1:c.784+1083G>A intron variant NM_001408400.1:c.784+1083G>A intron variant NM_001408401.1:c.784+1083G>A intron variant NM_001408402.1:c.784+1083G>A intron variant NM_001408403.1:c.787+1083G>A intron variant NM_001408404.1:c.787+1083G>A intron variant NM_001408406.1:c.790+1080G>A intron variant NM_001408407.1:c.784+1083G>A intron variant NM_001408408.1:c.778+1083G>A intron variant NM_001408409.1:c.709+1083G>A intron variant NM_001408410.1:c.646+1083G>A intron variant NM_001408411.1:c.709+1083G>A intron variant NM_001408412.1:c.709+1083G>A intron variant NM_001408413.1:c.706+1083G>A intron variant NM_001408414.1:c.709+1083G>A intron variant NM_001408415.1:c.709+1083G>A intron variant NM_001408416.1:c.706+1083G>A intron variant NM_001408418.1:c.670+2185G>A intron variant NM_001408419.1:c.670+2185G>A intron variant NM_001408420.1:c.670+2185G>A intron variant NM_001408421.1:c.667+2185G>A intron variant NM_001408422.1:c.670+2185G>A intron variant NM_001408423.1:c.670+2185G>A intron variant NM_001408424.1:c.667+2185G>A intron variant NM_001408425.1:c.664+1083G>A intron variant NM_001408426.1:c.664+1083G>A intron variant NM_001408427.1:c.664+1083G>A intron variant NM_001408428.1:c.664+1083G>A intron variant NM_001408429.1:c.664+1083G>A intron variant NM_001408430.1:c.664+1083G>A intron variant NM_001408431.1:c.667+2185G>A intron variant NM_001408432.1:c.661+1083G>A intron variant NM_001408433.1:c.661+1083G>A intron variant NM_001408434.1:c.661+1083G>A intron variant NM_001408435.1:c.661+1083G>A intron variant NM_001408436.1:c.664+1083G>A intron variant NM_001408437.1:c.664+1083G>A intron variant NM_001408438.1:c.664+1083G>A intron variant NM_001408439.1:c.664+1083G>A intron variant NM_001408440.1:c.664+1083G>A intron variant NM_001408441.1:c.664+1083G>A intron variant NM_001408442.1:c.664+1083G>A intron variant NM_001408443.1:c.664+1083G>A intron variant NM_001408444.1:c.664+1083G>A intron variant NM_001408445.1:c.661+1083G>A intron variant NM_001408446.1:c.661+1083G>A intron variant NM_001408447.1:c.661+1083G>A intron variant NM_001408448.1:c.661+1083G>A intron variant NM_001408450.1:c.661+1083G>A intron variant NM_001408451.1:c.652+1083G>A intron variant NM_001408452.1:c.646+1083G>A intron variant NM_001408453.1:c.646+1083G>A intron variant NM_001408454.1:c.646+1083G>A intron variant NM_001408455.1:c.646+1083G>A intron variant NM_001408456.1:c.646+1083G>A intron variant NM_001408457.1:c.646+1083G>A intron variant NM_001408458.1:c.646+1083G>A intron variant NM_001408459.1:c.646+1083G>A intron variant NM_001408460.1:c.646+1083G>A intron variant NM_001408461.1:c.646+1083G>A intron variant NM_001408462.1:c.643+1083G>A intron variant NM_001408463.1:c.643+1083G>A intron variant NM_001408464.1:c.643+1083G>A intron variant NM_001408465.1:c.643+1083G>A intron variant NM_001408466.1:c.646+1083G>A intron variant NM_001408467.1:c.646+1083G>A intron variant NM_001408468.1:c.643+1083G>A intron variant NM_001408469.1:c.646+1083G>A intron variant NM_001408470.1:c.643+1083G>A intron variant NM_001408472.1:c.787+1083G>A intron variant NM_001408473.1:c.784+1083G>A intron variant NM_001408474.1:c.586+1083G>A intron variant NM_001408475.1:c.583+1083G>A intron variant NM_001408476.1:c.586+1083G>A intron variant NM_001408478.1:c.577+1083G>A intron variant NM_001408479.1:c.577+1083G>A intron variant NM_001408480.1:c.577+1083G>A intron variant NM_001408481.1:c.577+1083G>A intron variant NM_001408482.1:c.577+1083G>A intron variant NM_001408483.1:c.577+1083G>A intron variant NM_001408484.1:c.577+1083G>A intron variant NM_001408485.1:c.577+1083G>A intron variant NM_001408489.1:c.577+1083G>A intron variant NM_001408490.1:c.574+1083G>A intron variant NM_001408491.1:c.574+1083G>A intron variant NM_001408492.1:c.577+1083G>A intron variant NM_001408493.1:c.574+1083G>A intron variant NM_001408494.1:c.548-2629G>A intron variant NM_001408495.1:c.545-2629G>A intron variant NM_001408496.1:c.523+1083G>A intron variant NM_001408497.1:c.523+1083G>A intron variant NM_001408498.1:c.523+1083G>A intron variant NM_001408499.1:c.523+1083G>A intron variant NM_001408500.1:c.523+1083G>A intron variant NM_001408501.1:c.523+1083G>A intron variant NM_001408502.1:c.454+1083G>A intron variant NM_001408503.1:c.520+1083G>A intron variant NM_001408504.1:c.520+1083G>A intron variant NM_001408505.1:c.520+1083G>A intron variant NM_001408506.1:c.460+2185G>A intron variant NM_001408507.1:c.460+2185G>A intron variant NM_001408508.1:c.451+1083G>A intron variant NM_001408509.1:c.451+1083G>A intron variant NM_001408510.1:c.406+1083G>A intron variant NM_001408511.1:c.404-2629G>A intron variant NM_001408512.1:c.283+1083G>A intron variant NM_001408513.1:c.577+1083G>A intron variant NM_001408514.1:c.577+1083G>A intron variant NM_007297.4:c.1729G>A NP_009228.2:p.Glu577Lys missense NM_007298.4:c.787+1083G>A intron variant NM_007299.4:c.787+1083G>A intron variant NM_007300.4:c.1870G>A NP_009231.2:p.Glu624Lys missense NR_027676.1:n.2006G>A NC_000017.11:g.43093661C>T NC_000017.10:g.41245678C>T NG_005905.2:g.124323G>A LRG_292:g.124323G>A LRG_292t1:c.1870G>A LRG_292p1:p.Glu624Lys U14680.1:n.1989G>A - Protein change
- E624K, E577K, E456K, E583K, E623K, E328K, E512K, E556K, E557K, E576K, E621K, E497K, E535K, E582K, E598K, E496K, E513K, E536K, E553K, E554K, E597K
- Other names
- -
- Canonical SPDI
- NC_000017.11:43093660:C:T
-
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) |
no assertion criteria provided
|
May 29, 2002 | RCV000111702.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 14, 2018 | RCV001308727.8 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 23, 2023 | RCV003157338.3 |
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: SCV003849678.1
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
(Sep 14, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001498196.4
First in ClinVar: Mar 07, 2021 Last updated: Feb 14, 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 54374). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 624 of the BRCA1 protein (p.Glu624Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. (less)
|
|
|
Uncertain significance
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144205.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
|
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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 54374). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 624 of the BRCA1 protein (p.Glu624Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine.
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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 54374). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 624 of the BRCA1 protein (p.Glu624Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine.
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 |
| LOVD v.2.0: the next generation in gene variant databases. | Fokkema IF | Human mutation | 2011 | PMID: 21520333 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Text-mined citations for rs80356950 ...
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.