ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.379C>T (p.Arg127Cys) (rs771113424)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000220615 SCV000272215 uncertain significance not specified 2015-06-09 criteria provided, single submitter clinical testing The p.Arg127Cys variant in NEXN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/16510 South Asian chromosomes and 2/66726 European chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org). Computational prediction tools and conservation ana lysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical si gnificance of the p.Arg127Cys variant is uncertain.
Invitae RCV000704647 SCV000833603 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2018-04-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 127 of the NEXN protein (p.Arg127Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs771113424, ExAC 0.01%). This variant has not been reported in the literature in individuals with NEXN-related disease. ClinVar contains an entry for this variant (Variation ID: 229058). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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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