ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.586C>T (p.Arg196Cys) (rs369486891)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155781 SCV000205492 uncertain significance not specified 2013-06-12 criteria provided, single submitter clinical testing The Arg196Cys in NEXN has not been reported in individuals with cardiomyopathy, but has been identified in 1/8146 European American chromosomes by the NHLBI Exo me Sequencing Project (http://evs.gs.washington.edu/EVS/). The affected amino ac id is not well conserved in evolution, raising the possibility that a change wou ld be tolerated. Other computational analyses (biochemical amino acid propertie s, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the c linical significance of this variant.
Invitae RCV000647286 SCV000769075 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2017-11-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 196 of the NEXN protein (p.Arg196Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs369486891, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with NEXN-related disease. ClinVar contains an entry for this variant (Variation ID: 179003). 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: "Tolerated"; 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768803 SCV000900175 uncertain significance Cardiomyopathy 2015-10-15 criteria provided, single submitter clinical testing

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