ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2434A>C (p.Lys812Gln)

gnomAD frequency: 0.00002  dbSNP: rs763827222
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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 RCV000628656 SCV000749560 uncertain significance Bloom syndrome 2023-11-17 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 812 of the BLM protein (p.Lys812Gln). This variant is present in population databases (rs763827222, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 524792). 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 expected to disrupt BLM protein function with a positive predictive value of 80%. 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 RCV001015520 SCV001176363 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-11 criteria provided, single submitter clinical testing The p.K812Q variant (also known as c.2434A>C), located in coding exon 11 of the BLM gene, results from an A to C substitution at nucleotide position 2434. The lysine at codon 812 is replaced by glutamine, an amino acid with similar properties. This amino acid position is highly 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.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153768 SCV003843783 likely pathogenic Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV000628656 SCV001461107 uncertain significance Bloom syndrome 2020-01-24 no assertion criteria provided clinical testing

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