Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
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; Hypertrophic cardiomyopathy 20 | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 510 of the NEXN protein (p.Lys510Arg). This variant is present in population databases (rs759726867, gnomAD 0.004%). 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: 870088). 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. 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. |
Ambry Genetics | RCV002402489 | SCV002705488 | uncertain significance | Cardiovascular phenotype | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.K510R variant (also known as c.1529A>G), located in coding exon 11 of the NEXN gene, results from an A to G substitution at nucleotide position 1529. The lysine at codon 510 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |