This sequence change replaces glutamic acid with aspartic acid at codon 1536 of the BRCA1 protein (p.Glu1536Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4608G>T (p.Glu1536Asp)
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
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.4608G>T (p.Glu1536Asp)
Variation ID: 1022166 Accession: VCV001022166.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074398 (GRCh38) [ NCBI UCSC ] 17: 41226415 (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 Mar 14, 2021 Jun 17, 2024 Feb 19, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4608G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1536Asp missense NM_001407571.1:c.4395G>T NP_001394500.1:p.Glu1465Asp missense NM_001407581.1:c.4674G>T NP_001394510.1:p.Glu1558Asp missense NM_001407582.1:c.4674G>T NP_001394511.1:p.Glu1558Asp missense NM_001407583.1:c.4671G>T NP_001394512.1:p.Glu1557Asp missense NM_001407585.1:c.4671G>T NP_001394514.1:p.Glu1557Asp missense NM_001407587.1:c.4671G>T NP_001394516.1:p.Glu1557Asp missense NM_001407590.1:c.4668G>T NP_001394519.1:p.Glu1556Asp missense NM_001407591.1:c.4668G>T NP_001394520.1:p.Glu1556Asp missense NM_001407593.1:c.4608G>T NP_001394522.1:p.Glu1536Asp missense NM_001407594.1:c.4608G>T NP_001394523.1:p.Glu1536Asp missense NM_001407596.1:c.4608G>T NP_001394525.1:p.Glu1536Asp missense NM_001407597.1:c.4608G>T NP_001394526.1:p.Glu1536Asp missense NM_001407598.1:c.4608G>T NP_001394527.1:p.Glu1536Asp missense NM_001407602.1:c.4608G>T NP_001394531.1:p.Glu1536Asp missense NM_001407603.1:c.4608G>T NP_001394532.1:p.Glu1536Asp missense NM_001407605.1:c.4608G>T NP_001394534.1:p.Glu1536Asp missense NM_001407610.1:c.4605G>T NP_001394539.1:p.Glu1535Asp missense NM_001407611.1:c.4605G>T NP_001394540.1:p.Glu1535Asp missense NM_001407612.1:c.4605G>T NP_001394541.1:p.Glu1535Asp missense NM_001407613.1:c.4605G>T NP_001394542.1:p.Glu1535Asp missense NM_001407614.1:c.4605G>T NP_001394543.1:p.Glu1535Asp missense NM_001407615.1:c.4605G>T NP_001394544.1:p.Glu1535Asp missense NM_001407616.1:c.4605G>T NP_001394545.1:p.Glu1535Asp missense NM_001407617.1:c.4605G>T NP_001394546.1:p.Glu1535Asp missense NM_001407618.1:c.4605G>T NP_001394547.1:p.Glu1535Asp missense NM_001407619.1:c.4605G>T NP_001394548.1:p.Glu1535Asp missense NM_001407620.1:c.4605G>T NP_001394549.1:p.Glu1535Asp missense NM_001407621.1:c.4605G>T NP_001394550.1:p.Glu1535Asp missense NM_001407622.1:c.4605G>T NP_001394551.1:p.Glu1535Asp missense NM_001407623.1:c.4605G>T NP_001394552.1:p.Glu1535Asp missense NM_001407624.1:c.4605G>T NP_001394553.1:p.Glu1535Asp missense NM_001407625.1:c.4605G>T NP_001394554.1:p.Glu1535Asp missense NM_001407626.1:c.4605G>T NP_001394555.1:p.Glu1535Asp missense NM_001407627.1:c.4602G>T NP_001394556.1:p.Glu1534Asp missense NM_001407628.1:c.4602G>T NP_001394557.1:p.Glu1534Asp missense NM_001407629.1:c.4602G>T NP_001394558.1:p.Glu1534Asp missense NM_001407630.1:c.4602G>T NP_001394559.1:p.Glu1534Asp missense NM_001407631.1:c.4602G>T NP_001394560.1:p.Glu1534Asp missense NM_001407632.1:c.4602G>T NP_001394561.1:p.Glu1534Asp missense NM_001407633.1:c.4602G>T NP_001394562.1:p.Glu1534Asp missense NM_001407634.1:c.4602G>T NP_001394563.1:p.Glu1534Asp missense NM_001407635.1:c.4602G>T NP_001394564.1:p.Glu1534Asp missense NM_001407636.1:c.4602G>T NP_001394565.1:p.Glu1534Asp missense NM_001407637.1:c.4602G>T NP_001394566.1:p.Glu1534Asp missense NM_001407638.1:c.4602G>T NP_001394567.1:p.Glu1534Asp missense NM_001407639.1:c.4602G>T NP_001394568.1:p.Glu1534Asp missense NM_001407640.1:c.4602G>T NP_001394569.1:p.Glu1534Asp missense NM_001407641.1:c.4602G>T NP_001394570.1:p.Glu1534Asp missense NM_001407642.1:c.4602G>T NP_001394571.1:p.Glu1534Asp missense NM_001407644.1:c.4599G>T NP_001394573.1:p.Glu1533Asp missense NM_001407645.1:c.4599G>T NP_001394574.1:p.Glu1533Asp missense NM_001407646.1:c.4596G>T NP_001394575.1:p.Glu1532Asp missense NM_001407647.1:c.4593G>T NP_001394576.1:p.Glu1531Asp missense NM_001407648.1:c.4551G>T NP_001394577.1:p.Glu1517Asp missense NM_001407649.1:c.4548G>T NP_001394578.1:p.Glu1516Asp missense NM_001407652.1:c.4608G>T NP_001394581.1:p.Glu1536Asp missense NM_001407653.1:c.4530G>T NP_001394582.1:p.Glu1510Asp missense NM_001407654.1:c.4530G>T NP_001394583.1:p.Glu1510Asp missense NM_001407655.1:c.4530G>T NP_001394584.1:p.Glu1510Asp missense NM_001407656.1:c.4527G>T NP_001394585.1:p.Glu1509Asp missense NM_001407657.1:c.4527G>T NP_001394586.1:p.Glu1509Asp missense NM_001407658.1:c.4527G>T NP_001394587.1:p.Glu1509Asp missense NM_001407659.1:c.4524G>T NP_001394588.1:p.Glu1508Asp missense NM_001407660.1:c.4524G>T NP_001394589.1:p.Glu1508Asp missense NM_001407661.1:c.4524G>T NP_001394590.1:p.Glu1508Asp missense NM_001407662.1:c.4524G>T NP_001394591.1:p.Glu1508Asp missense NM_001407663.1:c.4524G>T NP_001394592.1:p.Glu1508Asp missense NM_001407664.1:c.4485G>T NP_001394593.1:p.Glu1495Asp missense NM_001407665.1:c.4485G>T NP_001394594.1:p.Glu1495Asp missense NM_001407666.1:c.4485G>T NP_001394595.1:p.Glu1495Asp missense NM_001407667.1:c.4485G>T NP_001394596.1:p.Glu1495Asp missense NM_001407668.1:c.4485G>T NP_001394597.1:p.Glu1495Asp missense NM_001407669.1:c.4485G>T NP_001394598.1:p.Glu1495Asp missense NM_001407670.1:c.4482G>T NP_001394599.1:p.Glu1494Asp missense NM_001407671.1:c.4482G>T NP_001394600.1:p.Glu1494Asp missense NM_001407672.1:c.4482G>T NP_001394601.1:p.Glu1494Asp missense NM_001407673.1:c.4482G>T NP_001394602.1:p.Glu1494Asp missense NM_001407674.1:c.4482G>T NP_001394603.1:p.Glu1494Asp missense NM_001407675.1:c.4482G>T NP_001394604.1:p.Glu1494Asp missense NM_001407676.1:c.4482G>T NP_001394605.1:p.Glu1494Asp missense NM_001407677.1:c.4482G>T NP_001394606.1:p.Glu1494Asp missense NM_001407678.1:c.4482G>T NP_001394607.1:p.Glu1494Asp missense NM_001407679.1:c.4482G>T NP_001394608.1:p.Glu1494Asp missense NM_001407680.1:c.4482G>T NP_001394609.1:p.Glu1494Asp missense NM_001407681.1:c.4479G>T NP_001394610.1:p.Glu1493Asp missense NM_001407682.1:c.4479G>T NP_001394611.1:p.Glu1493Asp missense NM_001407683.1:c.4479G>T NP_001394612.1:p.Glu1493Asp missense NM_001407684.1:c.4608G>T NP_001394613.1:p.Glu1536Asp missense NM_001407685.1:c.4479G>T NP_001394614.1:p.Glu1493Asp missense NM_001407686.1:c.4479G>T NP_001394615.1:p.Glu1493Asp missense NM_001407687.1:c.4479G>T NP_001394616.1:p.Glu1493Asp missense NM_001407688.1:c.4479G>T NP_001394617.1:p.Glu1493Asp missense NM_001407689.1:c.4479G>T NP_001394618.1:p.Glu1493Asp missense NM_001407690.1:c.4476G>T NP_001394619.1:p.Glu1492Asp missense NM_001407691.1:c.4476G>T NP_001394620.1:p.Glu1492Asp missense NM_001407692.1:c.4467G>T NP_001394621.1:p.Glu1489Asp missense NM_001407694.1:c.4467G>T NP_001394623.1:p.Glu1489Asp missense NM_001407695.1:c.4467G>T NP_001394624.1:p.Glu1489Asp missense NM_001407696.1:c.4467G>T NP_001394625.1:p.Glu1489Asp missense NM_001407697.1:c.4467G>T NP_001394626.1:p.Glu1489Asp missense NM_001407698.1:c.4467G>T NP_001394627.1:p.Glu1489Asp missense NM_001407724.1:c.4467G>T NP_001394653.1:p.Glu1489Asp missense NM_001407725.1:c.4467G>T NP_001394654.1:p.Glu1489Asp missense NM_001407726.1:c.4467G>T NP_001394655.1:p.Glu1489Asp missense NM_001407727.1:c.4467G>T NP_001394656.1:p.Glu1489Asp missense NM_001407728.1:c.4467G>T NP_001394657.1:p.Glu1489Asp missense NM_001407729.1:c.4467G>T NP_001394658.1:p.Glu1489Asp missense NM_001407730.1:c.4467G>T NP_001394659.1:p.Glu1489Asp missense NM_001407731.1:c.4467G>T NP_001394660.1:p.Glu1489Asp missense NM_001407732.1:c.4464G>T NP_001394661.1:p.Glu1488Asp missense NM_001407733.1:c.4464G>T NP_001394662.1:p.Glu1488Asp missense NM_001407734.1:c.4464G>T NP_001394663.1:p.Glu1488Asp missense NM_001407735.1:c.4464G>T NP_001394664.1:p.Glu1488Asp missense NM_001407736.1:c.4464G>T NP_001394665.1:p.Glu1488Asp missense NM_001407737.1:c.4464G>T NP_001394666.1:p.Glu1488Asp missense NM_001407738.1:c.4464G>T NP_001394667.1:p.Glu1488Asp missense NM_001407739.1:c.4464G>T NP_001394668.1:p.Glu1488Asp missense NM_001407740.1:c.4464G>T NP_001394669.1:p.Glu1488Asp missense NM_001407741.1:c.4464G>T NP_001394670.1:p.Glu1488Asp missense NM_001407742.1:c.4464G>T NP_001394671.1:p.Glu1488Asp missense NM_001407743.1:c.4464G>T NP_001394672.1:p.Glu1488Asp missense NM_001407744.1:c.4464G>T NP_001394673.1:p.Glu1488Asp missense NM_001407745.1:c.4464G>T NP_001394674.1:p.Glu1488Asp missense NM_001407746.1:c.4464G>T NP_001394675.1:p.Glu1488Asp missense NM_001407747.1:c.4464G>T NP_001394676.1:p.Glu1488Asp missense NM_001407748.1:c.4464G>T NP_001394677.1:p.Glu1488Asp missense NM_001407749.1:c.4464G>T NP_001394678.1:p.Glu1488Asp missense NM_001407750.1:c.4464G>T NP_001394679.1:p.Glu1488Asp missense NM_001407751.1:c.4464G>T NP_001394680.1:p.Glu1488Asp missense NM_001407752.1:c.4464G>T NP_001394681.1:p.Glu1488Asp missense NM_001407838.1:c.4461G>T NP_001394767.1:p.Glu1487Asp missense NM_001407839.1:c.4461G>T NP_001394768.1:p.Glu1487Asp missense NM_001407841.1:c.4461G>T NP_001394770.1:p.Glu1487Asp missense NM_001407842.1:c.4461G>T NP_001394771.1:p.Glu1487Asp missense NM_001407843.1:c.4461G>T NP_001394772.1:p.Glu1487Asp missense NM_001407844.1:c.4461G>T NP_001394773.1:p.Glu1487Asp missense NM_001407845.1:c.4461G>T NP_001394774.1:p.Glu1487Asp missense NM_001407846.1:c.4461G>T NP_001394775.1:p.Glu1487Asp missense NM_001407847.1:c.4461G>T NP_001394776.1:p.Glu1487Asp missense NM_001407848.1:c.4461G>T NP_001394777.1:p.Glu1487Asp missense NM_001407849.1:c.4461G>T NP_001394778.1:p.Glu1487Asp missense NM_001407850.1:c.4461G>T NP_001394779.1:p.Glu1487Asp missense NM_001407851.1:c.4461G>T NP_001394780.1:p.Glu1487Asp missense NM_001407852.1:c.4461G>T NP_001394781.1:p.Glu1487Asp missense NM_001407853.1:c.4461G>T NP_001394782.1:p.Glu1487Asp missense NM_001407854.1:c.4608G>T NP_001394783.1:p.Glu1536Asp missense NM_001407858.1:c.4605G>T NP_001394787.1:p.Glu1535Asp missense NM_001407859.1:c.4605G>T NP_001394788.1:p.Glu1535Asp missense NM_001407860.1:c.4605G>T NP_001394789.1:p.Glu1535Asp missense NM_001407861.1:c.4602G>T NP_001394790.1:p.Glu1534Asp missense NM_001407862.1:c.4407G>T NP_001394791.1:p.Glu1469Asp missense NM_001407863.1:c.4482G>T NP_001394792.1:p.Glu1494Asp missense NM_001407874.1:c.4401G>T NP_001394803.1:p.Glu1467Asp missense NM_001407875.1:c.4401G>T NP_001394804.1:p.Glu1467Asp missense NM_001407879.1:c.4398G>T NP_001394808.1:p.Glu1466Asp missense NM_001407881.1:c.4398G>T NP_001394810.1:p.Glu1466Asp missense NM_001407882.1:c.4398G>T NP_001394811.1:p.Glu1466Asp missense NM_001407884.1:c.4398G>T NP_001394813.1:p.Glu1466Asp missense NM_001407885.1:c.4398G>T NP_001394814.1:p.Glu1466Asp missense NM_001407886.1:c.4398G>T NP_001394815.1:p.Glu1466Asp missense NM_001407887.1:c.4398G>T NP_001394816.1:p.Glu1466Asp missense NM_001407889.1:c.4398G>T NP_001394818.1:p.Glu1466Asp missense NM_001407894.1:c.4395G>T NP_001394823.1:p.Glu1465Asp missense NM_001407895.1:c.4395G>T NP_001394824.1:p.Glu1465Asp missense NM_001407896.1:c.4395G>T NP_001394825.1:p.Glu1465Asp missense NM_001407897.1:c.4395G>T NP_001394826.1:p.Glu1465Asp missense NM_001407898.1:c.4395G>T NP_001394827.1:p.Glu1465Asp missense NM_001407899.1:c.4395G>T NP_001394828.1:p.Glu1465Asp missense NM_001407900.1:c.4395G>T NP_001394829.1:p.Glu1465Asp missense NM_001407902.1:c.4395G>T NP_001394831.1:p.Glu1465Asp missense NM_001407904.1:c.4395G>T NP_001394833.1:p.Glu1465Asp missense NM_001407906.1:c.4395G>T NP_001394835.1:p.Glu1465Asp missense NM_001407907.1:c.4395G>T NP_001394836.1:p.Glu1465Asp missense NM_001407908.1:c.4395G>T NP_001394837.1:p.Glu1465Asp missense NM_001407909.1:c.4395G>T NP_001394838.1:p.Glu1465Asp missense NM_001407910.1:c.4395G>T NP_001394839.1:p.Glu1465Asp missense NM_001407915.1:c.4392G>T NP_001394844.1:p.Glu1464Asp missense NM_001407916.1:c.4392G>T NP_001394845.1:p.Glu1464Asp missense NM_001407917.1:c.4392G>T NP_001394846.1:p.Glu1464Asp missense NM_001407918.1:c.4392G>T NP_001394847.1:p.Glu1464Asp missense NM_001407919.1:c.4485G>T NP_001394848.1:p.Glu1495Asp missense NM_001407920.1:c.4344G>T NP_001394849.1:p.Glu1448Asp missense NM_001407921.1:c.4344G>T NP_001394850.1:p.Glu1448Asp missense NM_001407922.1:c.4344G>T NP_001394851.1:p.Glu1448Asp missense NM_001407923.1:c.4344G>T NP_001394852.1:p.Glu1448Asp missense NM_001407924.1:c.4344G>T NP_001394853.1:p.Glu1448Asp missense NM_001407925.1:c.4344G>T NP_001394854.1:p.Glu1448Asp missense NM_001407926.1:c.4344G>T NP_001394855.1:p.Glu1448Asp missense NM_001407927.1:c.4341G>T NP_001394856.1:p.Glu1447Asp missense NM_001407928.1:c.4341G>T NP_001394857.1:p.Glu1447Asp missense NM_001407929.1:c.4341G>T NP_001394858.1:p.Glu1447Asp missense NM_001407930.1:c.4341G>T NP_001394859.1:p.Glu1447Asp missense NM_001407931.1:c.4341G>T NP_001394860.1:p.Glu1447Asp missense NM_001407932.1:c.4341G>T NP_001394861.1:p.Glu1447Asp missense NM_001407933.1:c.4341G>T NP_001394862.1:p.Glu1447Asp missense NM_001407934.1:c.4338G>T NP_001394863.1:p.Glu1446Asp missense NM_001407935.1:c.4338G>T NP_001394864.1:p.Glu1446Asp missense NM_001407936.1:c.4338G>T NP_001394865.1:p.Glu1446Asp missense NM_001407937.1:c.4485G>T NP_001394866.1:p.Glu1495Asp missense NM_001407938.1:c.4485G>T NP_001394867.1:p.Glu1495Asp missense NM_001407939.1:c.4482G>T NP_001394868.1:p.Glu1494Asp missense NM_001407940.1:c.4482G>T NP_001394869.1:p.Glu1494Asp missense NM_001407941.1:c.4479G>T NP_001394870.1:p.Glu1493Asp missense NM_001407942.1:c.4467G>T NP_001394871.1:p.Glu1489Asp missense NM_001407943.1:c.4464G>T NP_001394872.1:p.Glu1488Asp missense NM_001407944.1:c.4464G>T NP_001394873.1:p.Glu1488Asp missense NM_001407945.1:c.4464G>T NP_001394874.1:p.Glu1488Asp missense NM_001407946.1:c.4275G>T NP_001394875.1:p.Glu1425Asp missense NM_001407947.1:c.4275G>T NP_001394876.1:p.Glu1425Asp missense NM_001407948.1:c.4275G>T NP_001394877.1:p.Glu1425Asp missense NM_001407949.1:c.4275G>T NP_001394878.1:p.Glu1425Asp missense NM_001407950.1:c.4272G>T NP_001394879.1:p.Glu1424Asp missense NM_001407951.1:c.4272G>T NP_001394880.1:p.Glu1424Asp missense NM_001407952.1:c.4272G>T NP_001394881.1:p.Glu1424Asp missense NM_001407953.1:c.4272G>T NP_001394882.1:p.Glu1424Asp missense NM_001407954.1:c.4272G>T NP_001394883.1:p.Glu1424Asp missense NM_001407955.1:c.4272G>T NP_001394884.1:p.Glu1424Asp missense NM_001407956.1:c.4269G>T NP_001394885.1:p.Glu1423Asp missense NM_001407957.1:c.4269G>T NP_001394886.1:p.Glu1423Asp missense NM_001407958.1:c.4269G>T NP_001394887.1:p.Glu1423Asp missense NM_001407959.1:c.4227G>T NP_001394888.1:p.Glu1409Asp missense NM_001407960.1:c.4224G>T NP_001394889.1:p.Glu1408Asp missense NM_001407962.1:c.4224G>T NP_001394891.1:p.Glu1408Asp missense NM_001407963.1:c.4221G>T NP_001394892.1:p.Glu1407Asp missense NM_001407965.1:c.4101G>T NP_001394894.1:p.Glu1367Asp missense NM_001407966.1:c.3720G>T NP_001394895.1:p.Glu1240Asp missense NM_001407967.1:c.3717G>T NP_001394896.1:p.Glu1239Asp missense NM_001407968.1:c.2004G>T NP_001394897.1:p.Glu668Asp missense NM_001407969.1:c.2001G>T NP_001394898.1:p.Glu667Asp missense NM_001407970.1:c.1365G>T NP_001394899.1:p.Glu455Asp missense NM_001407971.1:c.1365G>T NP_001394900.1:p.Glu455Asp missense NM_001407972.1:c.1362G>T NP_001394901.1:p.Glu454Asp missense NM_001407973.1:c.1299G>T NP_001394902.1:p.Glu433Asp missense NM_001407974.1:c.1299G>T NP_001394903.1:p.Glu433Asp missense NM_001407975.1:c.1299G>T NP_001394904.1:p.Glu433Asp missense NM_001407976.1:c.1299G>T NP_001394905.1:p.Glu433Asp missense NM_001407977.1:c.1299G>T NP_001394906.1:p.Glu433Asp missense NM_001407978.1:c.1299G>T NP_001394907.1:p.Glu433Asp missense NM_001407979.1:c.1296G>T NP_001394908.1:p.Glu432Asp missense NM_001407980.1:c.1296G>T NP_001394909.1:p.Glu432Asp missense NM_001407981.1:c.1296G>T NP_001394910.1:p.Glu432Asp missense NM_001407982.1:c.1296G>T NP_001394911.1:p.Glu432Asp missense NM_001407983.1:c.1296G>T NP_001394912.1:p.Glu432Asp missense NM_001407984.1:c.1296G>T NP_001394913.1:p.Glu432Asp missense NM_001407985.1:c.1296G>T NP_001394914.1:p.Glu432Asp missense NM_001407986.1:c.1296G>T NP_001394915.1:p.Glu432Asp missense NM_001407990.1:c.1296G>T NP_001394919.1:p.Glu432Asp missense NM_001407991.1:c.1296G>T NP_001394920.1:p.Glu432Asp missense NM_001407992.1:c.1296G>T NP_001394921.1:p.Glu432Asp missense NM_001407993.1:c.1296G>T NP_001394922.1:p.Glu432Asp missense NM_001408392.1:c.1293G>T NP_001395321.1:p.Glu431Asp missense NM_001408396.1:c.1293G>T NP_001395325.1:p.Glu431Asp missense NM_001408397.1:c.1293G>T NP_001395326.1:p.Glu431Asp missense NM_001408398.1:c.1293G>T NP_001395327.1:p.Glu431Asp missense NM_001408399.1:c.1293G>T NP_001395328.1:p.Glu431Asp missense NM_001408400.1:c.1293G>T NP_001395329.1:p.Glu431Asp missense NM_001408401.1:c.1293G>T NP_001395330.1:p.Glu431Asp missense NM_001408402.1:c.1293G>T NP_001395331.1:p.Glu431Asp missense NM_001408403.1:c.1293G>T NP_001395332.1:p.Glu431Asp missense NM_001408404.1:c.1293G>T NP_001395333.1:p.Glu431Asp missense NM_001408406.1:c.1290G>T NP_001395335.1:p.Glu430Asp missense NM_001408407.1:c.1290G>T NP_001395336.1:p.Glu430Asp missense NM_001408408.1:c.1290G>T NP_001395337.1:p.Glu430Asp missense NM_001408409.1:c.1287G>T NP_001395338.1:p.Glu429Asp missense NM_001408410.1:c.1224G>T NP_001395339.1:p.Glu408Asp missense NM_001408411.1:c.1221G>T NP_001395340.1:p.Glu407Asp missense NM_001408412.1:c.1218G>T NP_001395341.1:p.Glu406Asp missense NM_001408413.1:c.1218G>T NP_001395342.1:p.Glu406Asp missense NM_001408414.1:c.1218G>T NP_001395343.1:p.Glu406Asp missense NM_001408415.1:c.1218G>T NP_001395344.1:p.Glu406Asp missense NM_001408416.1:c.1218G>T NP_001395345.1:p.Glu406Asp missense NM_001408418.1:c.1182G>T NP_001395347.1:p.Glu394Asp missense NM_001408419.1:c.1182G>T NP_001395348.1:p.Glu394Asp missense NM_001408420.1:c.1182G>T NP_001395349.1:p.Glu394Asp missense NM_001408421.1:c.1179G>T NP_001395350.1:p.Glu393Asp missense NM_001408422.1:c.1179G>T NP_001395351.1:p.Glu393Asp missense NM_001408423.1:c.1179G>T NP_001395352.1:p.Glu393Asp missense NM_001408424.1:c.1179G>T NP_001395353.1:p.Glu393Asp missense NM_001408425.1:c.1176G>T NP_001395354.1:p.Glu392Asp missense NM_001408426.1:c.1176G>T NP_001395355.1:p.Glu392Asp missense NM_001408427.1:c.1176G>T NP_001395356.1:p.Glu392Asp missense NM_001408428.1:c.1176G>T NP_001395357.1:p.Glu392Asp missense NM_001408429.1:c.1176G>T NP_001395358.1:p.Glu392Asp missense NM_001408430.1:c.1176G>T NP_001395359.1:p.Glu392Asp missense NM_001408431.1:c.1176G>T NP_001395360.1:p.Glu392Asp missense NM_001408432.1:c.1173G>T NP_001395361.1:p.Glu391Asp missense NM_001408433.1:c.1173G>T NP_001395362.1:p.Glu391Asp missense NM_001408434.1:c.1173G>T NP_001395363.1:p.Glu391Asp missense NM_001408435.1:c.1173G>T NP_001395364.1:p.Glu391Asp missense NM_001408436.1:c.1173G>T NP_001395365.1:p.Glu391Asp missense NM_001408437.1:c.1173G>T NP_001395366.1:p.Glu391Asp missense NM_001408438.1:c.1173G>T NP_001395367.1:p.Glu391Asp missense NM_001408439.1:c.1173G>T NP_001395368.1:p.Glu391Asp missense NM_001408440.1:c.1173G>T NP_001395369.1:p.Glu391Asp missense NM_001408441.1:c.1173G>T NP_001395370.1:p.Glu391Asp missense NM_001408442.1:c.1173G>T NP_001395371.1:p.Glu391Asp missense NM_001408443.1:c.1173G>T NP_001395372.1:p.Glu391Asp missense NM_001408444.1:c.1173G>T NP_001395373.1:p.Glu391Asp missense NM_001408445.1:c.1170G>T NP_001395374.1:p.Glu390Asp missense NM_001408446.1:c.1170G>T NP_001395375.1:p.Glu390Asp missense NM_001408447.1:c.1170G>T NP_001395376.1:p.Glu390Asp missense NM_001408448.1:c.1170G>T NP_001395377.1:p.Glu390Asp missense NM_001408450.1:c.1170G>T NP_001395379.1:p.Glu390Asp missense NM_001408451.1:c.1164G>T NP_001395380.1:p.Glu388Asp missense NM_001408452.1:c.1158G>T NP_001395381.1:p.Glu386Asp missense NM_001408453.1:c.1158G>T NP_001395382.1:p.Glu386Asp missense NM_001408454.1:c.1158G>T NP_001395383.1:p.Glu386Asp missense NM_001408455.1:c.1158G>T NP_001395384.1:p.Glu386Asp missense NM_001408456.1:c.1158G>T NP_001395385.1:p.Glu386Asp missense NM_001408457.1:c.1158G>T NP_001395386.1:p.Glu386Asp missense NM_001408458.1:c.1155G>T NP_001395387.1:p.Glu385Asp missense NM_001408459.1:c.1155G>T NP_001395388.1:p.Glu385Asp missense NM_001408460.1:c.1155G>T NP_001395389.1:p.Glu385Asp missense NM_001408461.1:c.1155G>T NP_001395390.1:p.Glu385Asp missense NM_001408462.1:c.1155G>T NP_001395391.1:p.Glu385Asp missense NM_001408463.1:c.1155G>T NP_001395392.1:p.Glu385Asp missense NM_001408464.1:c.1155G>T NP_001395393.1:p.Glu385Asp missense NM_001408465.1:c.1155G>T NP_001395394.1:p.Glu385Asp missense NM_001408466.1:c.1155G>T NP_001395395.1:p.Glu385Asp missense NM_001408467.1:c.1155G>T NP_001395396.1:p.Glu385Asp missense NM_001408468.1:c.1152G>T NP_001395397.1:p.Glu384Asp missense NM_001408469.1:c.1152G>T NP_001395398.1:p.Glu384Asp missense NM_001408470.1:c.1152G>T NP_001395399.1:p.Glu384Asp missense NM_001408472.1:c.1296G>T NP_001395401.1:p.Glu432Asp missense NM_001408473.1:c.1293G>T NP_001395402.1:p.Glu431Asp missense NM_001408474.1:c.1098G>T NP_001395403.1:p.Glu366Asp missense NM_001408475.1:c.1095G>T NP_001395404.1:p.Glu365Asp missense NM_001408476.1:c.1095G>T NP_001395405.1:p.Glu365Asp missense NM_001408478.1:c.1089G>T NP_001395407.1:p.Glu363Asp missense NM_001408479.1:c.1089G>T NP_001395408.1:p.Glu363Asp missense NM_001408480.1:c.1089G>T NP_001395409.1:p.Glu363Asp missense NM_001408481.1:c.1086G>T NP_001395410.1:p.Glu362Asp missense NM_001408482.1:c.1086G>T NP_001395411.1:p.Glu362Asp missense NM_001408483.1:c.1086G>T NP_001395412.1:p.Glu362Asp missense NM_001408484.1:c.1086G>T NP_001395413.1:p.Glu362Asp missense NM_001408485.1:c.1086G>T NP_001395414.1:p.Glu362Asp missense NM_001408489.1:c.1086G>T NP_001395418.1:p.Glu362Asp missense NM_001408490.1:c.1086G>T NP_001395419.1:p.Glu362Asp missense NM_001408491.1:c.1086G>T NP_001395420.1:p.Glu362Asp missense NM_001408492.1:c.1083G>T NP_001395421.1:p.Glu361Asp missense NM_001408493.1:c.1083G>T NP_001395422.1:p.Glu361Asp missense NM_001408494.1:c.1059G>T NP_001395423.1:p.Glu353Asp missense NM_001408495.1:c.1053G>T NP_001395424.1:p.Glu351Asp missense NM_001408496.1:c.1035G>T NP_001395425.1:p.Glu345Asp missense NM_001408497.1:c.1035G>T NP_001395426.1:p.Glu345Asp missense NM_001408498.1:c.1035G>T NP_001395427.1:p.Glu345Asp missense NM_001408499.1:c.1035G>T NP_001395428.1:p.Glu345Asp missense NM_001408500.1:c.1035G>T NP_001395429.1:p.Glu345Asp missense NM_001408501.1:c.1035G>T NP_001395430.1:p.Glu345Asp missense NM_001408502.1:c.1032G>T NP_001395431.1:p.Glu344Asp missense NM_001408503.1:c.1032G>T NP_001395432.1:p.Glu344Asp missense NM_001408504.1:c.1032G>T NP_001395433.1:p.Glu344Asp missense NM_001408505.1:c.1029G>T NP_001395434.1:p.Glu343Asp missense NM_001408506.1:c.972G>T NP_001395435.1:p.Glu324Asp missense NM_001408507.1:c.969G>T NP_001395436.1:p.Glu323Asp missense NM_001408508.1:c.960G>T NP_001395437.1:p.Glu320Asp missense NM_001408509.1:c.957G>T NP_001395438.1:p.Glu319Asp missense NM_001408510.1:c.918G>T NP_001395439.1:p.Glu306Asp missense NM_001408511.1:c.915G>T NP_001395440.1:p.Glu305Asp missense NM_001408512.1:c.795G>T NP_001395441.1:p.Glu265Asp missense NM_007297.4:c.4467G>T NP_009228.2:p.Glu1489Asp missense NM_007298.4:c.1296G>T NP_009229.2:p.Glu432Asp missense NM_007299.4:c.1296G>T NP_009230.2:p.Glu432Asp missense NM_007300.4:c.4671G>T NP_009231.2:p.Glu1557Asp missense NM_007304.2:c.1296G>T NP_009235.2:p.Glu432Asp missense NR_027676.2:n.4785G>T non-coding transcript variant NC_000017.11:g.43074398C>A NC_000017.10:g.41226415C>A NG_005905.2:g.143586G>T LRG_292:g.143586G>T LRG_292t1:c.4608G>T LRG_292p1:p.Glu1536Asp - Protein change
- E1489D, E1536D, E1557D, E432D, E1239D, E1425D, E1446D, E1464D, E1466D, E1487D, E1488D, E1493D, E1516D, E1517D, E306D, E320D, E323D, E324D, E351D, E361D, E362D, E386D, E390D, E392D, E406D, E408D, E430D, E667D, E1407D, E1409D, E1469D, E1508D, E1509D, E1510D, E1532D, E1558D, E305D, E344D, E345D, E366D, E384D, E385D, E393D, E431D, E668D, E1240D, E1367D, E1423D, E1424D, E1494D, E1531D, E1534D, E1535D, E1556D, E319D, E365D, E388D, E407D, E1408D, E1447D, E1448D, E1465D, E1467D, E1492D, E1495D, E1533D, E265D, E343D, E353D, E363D, E391D, E394D, E429D, E433D, E454D, E455D
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074397:C:A
-
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.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13041 | 14847 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 1, 2020 | RCV001322039.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 19, 2024 | RCV004570775.1 |
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
(Nov 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001512891.4
First in ClinVar: Mar 14, 2021 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces glutamic acid with aspartic acid at codon 1536 of the BRCA1 protein (p.Glu1536Asp). The glutamic acid residue is weakly conserved and … (more)
This sequence change replaces glutamic acid with aspartic acid at codon 1536 of the BRCA1 protein (p.Glu1536Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions. (less)
|
|
|
Uncertain significance
(Feb 19, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005058250.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This sequence change replaces glutamic acid with aspartic acid at codon 1536 of the BRCA1 protein (p.Glu1536Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs2052599261 ...
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.