ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1123G>C (p.Val375Leu)

dbSNP: rs1596228852
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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 RCV001009926 SCV001170055 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-22 criteria provided, single submitter clinical testing The p.V375L variant (also known as c.1123G>C), located in coding exon 5 of the BLM gene, results from a G to C substitution at nucleotide position 1123. The valine at codon 375 is replaced by leucine, an amino acid with highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001070931 SCV001236211 uncertain significance Bloom syndrome 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 375 of the BLM protein (p.Val375Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV002293497 SCV002586737 uncertain significance not provided 2022-04-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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