ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4300A>G (p.Lys1434Glu)

dbSNP: rs876659616
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216344 SCV000276275 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-05 criteria provided, single submitter clinical testing The p.K1434E variant (also known as c.4300A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4300. The lysine at codon 1434 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000637731 SCV000759204 uncertain significance Hereditary breast ovarian cancer syndrome 2024-07-17 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1434 of the BRCA2 protein (p.Lys1434Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 232205). 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 BRCA2 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000216344 SCV003850397 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).

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