ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2036A>C (p.Lys679Thr)

dbSNP: rs2053838870
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001040400 SCV001203972 uncertain significance Hereditary breast ovarian cancer syndrome 2023-04-04 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 679 of the BRCA1 protein (p.Lys679Thr). 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: 838783). 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. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158310 SCV003849554 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 RCV003158310 SCV005025795 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-27 criteria provided, single submitter clinical testing The p.K679T variant (also known as c.2036A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 2036. The lysine at codon 679 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998592 SCV005626027 uncertain significance not provided 2024-03-28 criteria provided, single submitter clinical testing The BRCA1 c.2036A>C (p.Lys679Thr) variant has not been reported in individuals with BRCA1-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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