ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1729A>C (p.Ser577Arg)

dbSNP: rs761955701
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001948331 SCV002198709 uncertain significance Bloom syndrome 2025-01-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 577 of the BLM protein (p.Ser577Arg). This variant is present in population databases (rs761955701, gnomAD 0.003%). 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: 1428669). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 RCV002407102 SCV002715638 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-10 criteria provided, single submitter clinical testing The p.S577R variant (also known as c.1729A>C), located in coding exon 6 of the BLM gene, results from an A to C substitution at nucleotide position 1729. The serine at codon 577 is replaced by arginine, an amino acid with dissimilar properties. 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.

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