ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1529A>G (p.Lys510Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV001089628 SCV001245105 uncertain significance Hypertrophic cardiomyopathy 2018-10-16 criteria provided, single submitter research NEXN Lys510Arg has not been previously reported but is present in population databases such as the Genome Aggregation Database (AF=0.000014; http://gnomad.broadinstitute.org/). We identified this variant in HCM proband with no family history of disease. In silico tools MutationTaster and PolyPhen2 predict this variant to be deleterious but SIFT predicts this variant to be 'tolerated'. Based on this information we classify this as a variant of 'uncertain significance'.
Invitae RCV001301329 SCV001490495 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-03-22 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 510 of the NEXN protein (p.Lys510Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs759726867, ExAC 0.003%). This variant has not been reported in the literature in individuals with NEXN-related conditions. 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: Possibly Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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