ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1625A>G (p.Asn542Ser)

dbSNP: rs2154433378
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001947125 SCV002131358 uncertain significance Hereditary breast ovarian cancer syndrome 2021-01-27 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. 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 asparagine with serine at codon 542 of the BRCA1 protein (p.Asn542Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine.
University of Washington Department of Laboratory Medicine, University of Washington RCV003159028 SCV003851163 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).
Ambry Genetics RCV003159028 SCV004058416 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-12 criteria provided, single submitter clinical testing The p.N542S variant (also known as c.1625A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1625. The asparagine at codon 542 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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