ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1831_1832delinsTA (p.Arg611Tyr) (rs863224266)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196564 SCV000252551 likely pathogenic not provided 2014-07-16 criteria provided, single submitter clinical testing The c.1831_1832delCGinsTA variant results in a R611Y amino acid change, which has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. The R611Y variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in an external variant database. The R611Y 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 highly conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant was interpreted to be a strong candidate for a pathogenic variant.
Invitae RCV000196564 SCV001559158 uncertain significance not provided 2020-10-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tyrosine at codon 611 of the WFS1 protein (p.Arg611Tyr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tyrosine. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This variant has not been reported in the literature in individuals with WFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 215407). 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: Not Available; PolyPhen-2: Possibly Damaging; Align-GVGD: Not Available). 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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