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

gnomAD frequency: 0.00009  dbSNP: rs397517858

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham 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; Hypertrophic cardiomyopathy 20	2022-05-19	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 131 of the NEXN protein (p.Gln131Arg). This variant is present in population databases (rs397517858, gnomAD 0.006%). This missense change has been observed in individual(s) 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.
Fulgent Genetics, Fulgent Genetics	RCV001240745	SCV002786588	uncertain significance	Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20	2022-02-22	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528610	SCV001740599	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528610	SCV001955089	uncertain significance	not provided		no assertion criteria provided	clinical testing