ClinVar Miner

Submissions for variant NM_004260.3(RECQL4):c.1885C>T (p.Arg629Trp) (rs772074149)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522443 SCV000619109 uncertain significance not provided 2017-07-25 criteria provided, single submitter clinical testing The R629W variant in the RECQL4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R629W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R629W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R629W as a variant of uncertain significance.
Invitae RCV000685813 SCV000813311 uncertain significance Baller-Gerold syndrome 2018-03-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 629 of the RECQL4 protein (p.Arg629Gln). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs772074149, ExAC 0.05%). This variant has not been reported in the literature in individuals with RECQL4-related disease. ClinVar contains an entry for this variant (Variation ID: 450513). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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