Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001063819 | SCV001228682 | uncertain significance | Brugada syndrome | 2021-09-04 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 306 of the SCN5A protein (p.Leu306Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs748956841, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 |
RCV001552115 | SCV001772755 | uncertain significance | not provided | 2020-01-21 | 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, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
ARUP Laboratories, |
RCV001552115 | SCV002049886 | uncertain significance | not provided | 2021-03-02 | criteria provided, single submitter | clinical testing | The SCN5A c.916C>G; p.Leu306Val variant (rs748956841), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 858024). This variant is found in the general population with an allele frequency of 0.0016% (4/248564alleles) in the Genome Aggregation Database. The leucine at codon 306 is weakly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.299). However, given the lack of clinical and functional data, the significance of the p.Leu306Val variant is uncertain at this time. |