ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1433G>C (p.Gly478Ala)

gnomAD frequency: 0.00001  dbSNP: rs759810567
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000537347 SCV000623237 uncertain significance Bloom syndrome 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 478 of the BLM protein (p.Gly478Ala). This variant is present in population databases (rs759810567, 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: 454076). 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 RCV000566609 SCV000672924 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-28 criteria provided, single submitter clinical testing The p.G478A variant (also known as c.1433G>C), located in coding exon 6 of the BLM gene, results from a G to C substitution at nucleotide position 1433. The glycine at codon 478 is replaced by alanine, an amino acid with similar 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.
Genome-Nilou Lab RCV000537347 SCV001781336 uncertain significance Bloom syndrome 2021-07-14 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000566609 SCV002531327 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-19 criteria provided, single submitter curation
GeneDx RCV002291652 SCV002584091 uncertain significance not provided 2022-04-15 criteria provided, single submitter clinical testing 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
Natera, Inc. RCV000537347 SCV002090038 uncertain significance Bloom syndrome 2018-04-23 no assertion criteria provided clinical testing

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