ClinVar Miner

Submissions for variant NM_016373.4(WWOX):c.341T>C (p.Met114Thr) (rs761906386)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658343 SCV000780115 uncertain significance not provided 2018-05-23 criteria provided, single submitter clinical testing The M114T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M114T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The M114T 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 and evolutionary 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 RCV000696611 SCV000825177 uncertain significance Epileptic encephalopathy, early infantile, 1; Spinocerebellar ataxia, autosomal recessive 12 2018-07-11 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 114 of the WWOX protein (p.Met114Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with WWOX-related disease. 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 tolerated, 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.
Fulgent Genetics,Fulgent Genetics RCV000764077 SCV000895038 uncertain significance Malignant tumor of esophagus; Spinocerebellar ataxia, autosomal recessive 12; Epileptic encephalopathy, early infantile, 28 2018-10-31 criteria provided, single submitter clinical testing

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