ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1496C>T (p.Ser499Phe)

gnomAD frequency: 0.00001  dbSNP: rs778700833
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000226684 SCV000283115 uncertain significance Bloom syndrome 2024-12-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 499 of the BLM protein (p.Ser499Phe). This variant is present in population databases (rs778700833, gnomAD 0.004%). 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: 236803). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BLM protein function with a negative 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 RCV001011785 SCV001172147 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-30 criteria provided, single submitter clinical testing The p.S499F variant (also known as c.1496C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1496. The serine at codon 499 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237781 SCV002010768 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003237781 SCV004222432 uncertain significance not provided 2023-08-30 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in an individual with breast cancer (PMID: 37316882 (2023)). The frequency of this variant in the general population, 0.000035 (4/113040 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000226684 SCV001460785 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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