ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1337C>T (p.Thr446Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002387616 SCV002691852 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-06 criteria provided, single submitter clinical testing The p.T446I variant (also known as c.1337C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1337. The threonine at codon 446 is replaced by isoleucine, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094990 SCV002965192 uncertain significance Bloom syndrome 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 446 of the BLM protein (p.Thr446Ile). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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