ClinVar Miner

Submissions for variant NM_016373.4(WWOX):c.499C>T (p.Arg167Cys) (rs201228765)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498364 SCV000590280 uncertain significance not provided 2017-12-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the WWOX gene. The R167C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to ourknowledge. The R167C variant is observed in 12/24016 (0.05%) alleles from individuals of Africanbackground in large population cohorts (Lek et al., 2016). The R167C 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. In-silico analyses, including protein predictors andevolutionary conservation, support a deleterious effect. Based on the currently available information,it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000699068 SCV000827763 uncertain significance Epileptic encephalopathy, early infantile, 1; Spinocerebellar ataxia, autosomal recessive 12 2018-05-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 167 of the WWOX protein (p.Arg167Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs201228765, ExAC 0.06%). This variant has not been reported in the literature in individuals with WWOX-related disease. ClinVar contains an entry for this variant (Variation ID: 432543). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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