ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.242A>T (p.Asp81Val)

gnomAD frequency: 0.00028  dbSNP: rs367871780
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183648 SCV000236117 uncertain significance not provided 2022-11-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign in association with cardiomyopathy to our knowledge; This variant is associated with the following publications: (PMID: 32579932)
Labcorp Genetics (formerly Invitae), Labcorp RCV000647282 SCV000769071 uncertain significance Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 2022-09-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 81 of the NEXN protein (p.Asp81Val). This variant is present in population databases (rs367871780, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 201915). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195577 SCV001365971 likely benign not specified 2019-04-17 criteria provided, single submitter clinical testing The p.Asp81Val variant in NEXN is classified as likely benign because it has been identified in 0.06% (15/24194) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1.
Ambry Genetics RCV002444744 SCV002735281 uncertain significance Cardiovascular phenotype 2023-11-20 criteria provided, single submitter clinical testing The p.D81V variant (also known as c.242A>T), located in coding exon 3 of the NEXN gene, results from an A to T substitution at nucleotide position 242. The aspartic acid at codon 81 is replaced by valine, an amino acid with highly dissimilar properties. This variant has been detected in an individual indicated as having dilated cardiomyopathy; however, details were limited (VanDyke RE et al. J Genet Couns. 2021 Apr;30(2):503-512). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678728 SCV000804900 uncertain significance Left ventricular hypertrophy 2015-11-25 no assertion criteria provided clinical testing

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