ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4772G>A (p.Gly1591Asp)

dbSNP: rs1555580956
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540999 SCV000635994 uncertain significance Hereditary breast ovarian cancer syndrome 2017-01-23 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. This sequence change replaces glycine with aspartic acid at codon 1591 of the BRCA1 protein (p.Gly1591Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001805163 SCV002053695 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-14 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 1591 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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