ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.242A>T (p.Asp81Val) (rs367871780)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183648 SCV000236117 uncertain significance not provided 2016-02-05 criteria provided, single submitter clinical testing The D81V variant in the NEXN gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports D81V was observed in 3/3624 alleles from individuals of African American background. The D81V variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Another missense mutation (Q131E) has been reported in association with cardiomyopathy, but no mutations are in close proximity to residue Asp 81. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000647282 SCV000769071 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2017-12-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 81 of the NEXN protein (p.Asp81Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs367871780, ExAC 0.03%). This variant has not been reported in the literature in individuals with NEXN-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
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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