ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1675G>A (p.Gly559Ser)

dbSNP: rs1555591384
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528590 SCV000635806 uncertain significance Hereditary breast ovarian cancer syndrome 2024-09-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 559 of the BRCA1 protein (p.Gly559Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 462565). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV000777272 SCV000912974 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000777272 SCV002712779 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-04 criteria provided, single submitter clinical testing The p.G559S variant (also known as c.1675G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1675. The glycine at codon 559 is replaced by serine, an amino acid with 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000777272 SCV003851125 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).
BRCAlab, Lund University RCV003493633 SCV004244118 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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