ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1220G>C (p.Arg407Thr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000811037 SCV000951282 uncertain significance Bloom syndrome 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 407 of the BLM protein (p.Arg407Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine. This variant also falls at the last nucleotide of exon 6 of the BLM coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BLM-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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