ClinVar Miner

Submissions for variant NM_016373.4(WWOX):c.406A>G (p.Ile136Val)

gnomAD frequency: 0.00009  dbSNP: rs193027041
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537303 SCV000652349 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 136 of the WWOX protein (p.Ile136Val). This variant is present in population databases (rs193027041, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with WWOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 473024). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WWOX protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Baylor Genetics RCV001330929 SCV001522788 uncertain significance Developmental and epileptic encephalopathy, 28 2019-12-27 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic RCV001507346 SCV001712862 uncertain significance not provided 2019-07-22 criteria provided, single submitter clinical testing
GeneDx RCV001507346 SCV001820407 likely benign not provided 2019-09-03 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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