ClinVar Miner

Submissions for variant NM_004260.3(RECQL4):c.1684C>T (p.Arg562Trp) (rs61759892)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233616 SCV000288186 uncertain significance Baller-Gerold syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 562 of the RECQL4 protein (p.Arg562Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs61759892, ExAC 0.09%). This variant has not been reported in the literature in individuals with RECQL4-related disease. ClinVar contains an entry for this variant (Variation ID: 135128). 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.
GeneDx RCV000767196 SCV000622037 uncertain significance not provided 2018-04-30 criteria provided, single submitter clinical testing The R562W variant in the RECQL4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R562W variant is observed in 21/30,682 (0.07%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The R562W 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. Although this substitution occurs at a position that is not conserved, in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R562W as a variant of uncertain significance.
ITMI RCV000121929 SCV000086134 not provided not specified 2013-09-19 no assertion provided reference population

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.