ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1903A>G (p.Asn635Asp)

dbSNP: rs1567797783
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000771181 SCV000903126 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002533984 SCV003467925 uncertain significance Hereditary breast ovarian cancer syndrome 2023-04-12 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 627654). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 635 of the BRCA1 protein (p.Asn635Asp).
University of Washington Department of Laboratory Medicine, University of Washington RCV000771181 SCV003849653 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
GeneDx RCV004788163 SCV005401456 uncertain significance not provided 2024-05-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 2022A>G; This variant is associated with the following publications: (PMID: 31131967, 15343273, 31911673, 16267036)
Ambry Genetics RCV000771181 SCV005547501 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-13 criteria provided, single submitter clinical testing The p.N635D variant (also known as c.1903A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1903. The asparagine at codon 635 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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