ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.1271C>T (p.Thr424Ile) (rs200442502)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183662 SCV000236131 uncertain significance not provided 2019-08-02 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID# 201924; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Invitae RCV000529099 SCV000648475 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2019-07-11 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 424 of the NEXN protein (p.Thr424Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs200442502, ExAC 0.002%). This variant has not been reported in the literature in individuals with a NEXN-related disease. ClinVar contains an entry for this variant (Variation ID: 201924). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, this variant has uncertain impact on NEXN function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170728 SCV001333331 uncertain significance Cardiomyopathy 2019-04-11 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001256887 SCV001433384 uncertain significance Dilated cardiomyopathy 1A 2020-01-31 criteria provided, single submitter clinical testing

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