Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000215086 | SCV000272208 | uncertain significance | not specified | 2015-07-02 | criteria provided, single submitter | clinical testing | The p.Arg397Gln variant in NEXN has not been previously reported in individuals with cardiomyopathy, but has been identified in 4/15976 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201806320). Computational prediction tools and conservation analysis do not p rovide strong support for or against an impact to the protein. In summary, the c linical significance of the p.Arg397Gln variant is uncertain. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769823 | SCV000901249 | uncertain significance | Cardiomyopathy | 2017-02-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001853472 | SCV002272715 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2022-05-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 397 of the NEXN protein (p.Arg397Gln). This variant is present in population databases (rs201806320, gnomAD 0.02%). 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: 229052). 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: "Probably Damaging"; 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. |
Gene |
RCV002288842 | SCV002578280 | uncertain significance | not provided | 2022-04-07 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
Ambry Genetics | RCV002338685 | SCV002640823 | uncertain significance | Cardiovascular phenotype | 2023-03-20 | criteria provided, single submitter | clinical testing | The p.R397Q variant (also known as c.1190G>A), located in coding exon 9 of the NEXN gene, results from a G to A substitution at nucleotide position 1190. The arginine at codon 397 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV001853472 | SCV002790506 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2021-09-23 | criteria provided, single submitter | clinical testing |