ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1453G>A (p.Glu485Lys) (rs368812830)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041161 SCV000064852 uncertain significance not specified 2014-02-13 criteria provided, single submitter clinical testing The Glu485Lys variant in NEXN has not been reported in the literature but has be en observed in our laboratory in 2 individuals with cardiomyopathy, one with HCM and a second pathogenic variant in MYBPC3 and this individual. This variant h as also been observed in 2/6536 European American chromosomes in a broad and not well clinically characterized population by the NHLBI Exome Sequencing Project ( Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Gl u485Lys variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. In summary, additional data is needed to f ully assess the clinical significance of the Glu485Lys variant.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994029 SCV001147319 uncertain significance not provided 2016-10-01 criteria provided, single submitter clinical testing
Invitae RCV001039945 SCV001203496 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-01-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 485 of the NEXN protein (p.Glu485Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs368812830, ExAC 0.009%). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 47891). 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: Deleterious; PolyPhen-2: Probably 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.
University of Washington Center for Mendelian Genomics, University of Washington RCV001257941 SCV001434751 uncertain significance Primary dilated cardiomyopathy no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000994029 SCV001741584 uncertain significance not provided no assertion criteria provided clinical testing

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