ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1631A>G (p.Glu544Gly)

dbSNP: rs1567041307
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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 RCV000693981 SCV000822405 uncertain significance Bloom syndrome 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 544 of the BLM protein (p.Glu544Gly). This variant is not present in population databases (gnomAD no frequency). 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: 572568). 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000693981 SCV002584553 uncertain significance Bloom syndrome 2022-08-15 criteria provided, single submitter clinical testing The BLM c.1631A>G (p.Glu544Gly) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Ambry Genetics RCV002397409 SCV002706976 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-05 criteria provided, single submitter clinical testing The p.E544G variant (also known as c.1631A>G), located in coding exon 6 of the BLM gene, results from an A to G substitution at nucleotide position 1631. The glutamic acid at codon 544 is replaced by glycine, an amino acid with similar properties. This amino acid position is poorly 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.
GeneDx RCV003442031 SCV004169820 uncertain significance not provided 2023-05-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV000693981 SCV002092380 uncertain significance Bloom syndrome 2018-10-04 no assertion criteria provided clinical testing

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