ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1964T>C (p.Met655Thr)

gnomAD frequency: 0.00002  dbSNP: rs748567176
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573356 SCV000672977 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-02 criteria provided, single submitter clinical testing The p.M655T variant (also known as c.1964T>C), located in coding exon 7 of the BLM gene, results from a T to C substitution at nucleotide position 1964. The methionine at codon 655 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 RCV000628613 SCV000749515 uncertain significance Bloom syndrome 2024-05-12 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 655 of the BLM protein (p.Met655Thr). This variant is present in population databases (rs748567176, gnomAD 0.01%). 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: 485343). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BLM protein function with a positive 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.
GeneDx RCV004783815 SCV005396267 uncertain significance not provided 2024-05-08 criteria provided, single submitter clinical testing 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; This variant is associated with the following publications: (PMID: 32704157)
Natera, Inc. RCV000628613 SCV002088018 uncertain significance Bloom syndrome 2018-09-02 no assertion criteria provided clinical testing

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