Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522306 | SCV000619000 | uncertain significance | not provided | 2017-07-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN5A gene. The M28L variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, M28L is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution also occurs at a position that is not conserved across species and leucine (L) is the wild-type residue at this position in at least one mammalian species. Finally, in silico analysis predicts this variant likely does not alter the protein structure/function. |
| Color Diagnostics, |
RCV001841412 | SCV002052173 | uncertain significance | Cardiac arrhythmia | 2021-03-18 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with leucine at codon 28 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |