Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256885 | SCV001433382 | uncertain significance | Dilated cardiomyopathy 1A | 2019-10-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001366799 | SCV001563115 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 358 of the NEXN protein (p.Pro358Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs755252743, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. 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 tolerated. 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 |
RCV001575281 | SCV001802241 | uncertain significance | not provided | 2020-02-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function |
Ambry Genetics | RCV003166585 | SCV003854155 | uncertain significance | Cardiovascular phenotype | 2023-12-27 | criteria provided, single submitter | clinical testing | The c.1073C>T (p.P358L) alteration is located in exon 10 (coding exon 9) of the NEXN gene. This alteration results from a C to T substitution at nucleotide position 1073, causing the proline (P) at amino acid position 358 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |