Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519889 | SCV000620573 | uncertain significance | not provided | 2019-07-10 | criteria provided, single submitter | clinical testing | Has not been previously reported as pathogenic or benign to our knowledge; Identified in individuals referred for cardiac genetic testing at GeneDx; however, one proband also harbored a pathogenic variant in another arrhythmia-related gene, and segregation data is limited at this time; Observed in 0.0049% (12/246096) of global alleles in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice algorithms and evolutionary conservation, predict the creation of a cryptic splice donor site upstream of the natural splice donor site for intron 9, which may affect splicing; however, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined; The majority of SCN10A variants reported in association with arrhythmia in HGMD are missense variants (Stenson et al., 2014) |
| Ambry Genetics | RCV002431489 | SCV002744307 | likely benign | Cardiovascular phenotype | 2022-09-02 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Labcorp Genetics |
RCV002528255 | SCV003300389 | uncertain significance | Brugada syndrome | 2022-03-28 | criteria provided, single submitter | clinical testing | This sequence change affects codon 370 of the SCN10A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SCN10A protein. This variant is present in population databases (rs267599808, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 451820). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235268 | SCV003933845 | benign | not specified | 2023-05-25 | criteria provided, single submitter | clinical testing |