ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3358G>A (p.Gly1120Arg) (rs139773499)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553710 SCV000623310 uncertain significance Bloom syndrome 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1120 of the BLM protein (p.Gly1120Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant also falls at the last nucleotide of exon 17 of the BLM coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs139773499, ExAC 0.01%). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 454137). Experimental studies have shown that this missense has only a modest effect on BLM protein function (PMID: 23129629, 26788541) 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 is not likely to affect RNA splicing, 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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