Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001318065 | SCV001508753 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2020-06-26 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 500 of the NEXN protein (p.Ala500Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). 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: "Benign"; 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. |
| Ambry Genetics | RCV003294275 | SCV003996113 | uncertain significance | Cardiovascular phenotype | 2023-06-06 | criteria provided, single submitter | clinical testing | The p.A500S variant (also known as c.1498G>T), located in coding exon 11 of the NEXN gene, results from a G to T substitution at nucleotide position 1498. The alanine at codon 500 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |