ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1073C>T (p.Pro358Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001256885 SCV001433382 uncertain significance Dilated cardiomyopathy 1A 2019-10-09 criteria provided, single submitter clinical testing
Invitae RCV001366799 SCV001563115 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-03-19 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 with NEXN-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx 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

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