ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2734A>C (p.Lys912Gln)

dbSNP: rs1555589048
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000637379 SCV000758835 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 912 of the BRCA1 protein (p.Lys912Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with endometrial carcinoma (PMID: 22811390). ClinVar contains an entry for this variant (Variation ID: 531231). 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 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.
Ambry Genetics RCV002438688 SCV002746102 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-08 criteria provided, single submitter clinical testing The p.K912Q variant (also known as c.2734A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 2734. The lysine at codon 912 is replaced by glutamine, an amino acid with similar properties. This variant has been detected in an individual with uterine serous carcinoma (Pennington KP et al. Cancer, 2013 Jan;119:332-8). 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. 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 RCV002438688 SCV003849395 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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