ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.392A>G (p.Gln131Arg) (rs397517858)

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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 RCV000041178 SCV000064869 uncertain significance not specified 2012-08-13 criteria provided, single submitter clinical testing The Gln131Arg variant in NEXN has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Gl n131Arg variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. A different variant at this position (Gln13 1Glu) has been identified in a family with HCM, suggesting that a change of this amino acid may not be tolerated (Wang 2010). Additional information is needed t o fully assess the clinical significance of the Gln131Arg variant.
Invitae RCV001240745 SCV001413715 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-01-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 131 of the NEXN protein (p.Gln131Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs397517858, ExAC 0.009%). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 47907). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001528610 SCV001740599 uncertain significance not provided no assertion criteria provided clinical testing

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