Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188921 | SCV000242551 | uncertain significance | not provided | 2017-01-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN1A gene. The V1186L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V1186L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution alters a position where amino acids with similar properties to Valine are tolerated across species, and is predicted to be within the cytoplasmic loop between 2nd and 3rd homologous domains. However, the V1186L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001407708 | SCV001609687 | likely benign | Early infantile epileptic encephalopathy with suppression bursts | 2022-10-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002517888 | SCV003742226 | likely benign | Inborn genetic diseases | 2022-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |