Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000598919 | SCV000709847 | uncertain significance | not provided | 2018-05-03 | criteria provided, single submitter | clinical testing | The R1588X variant has not been published as a pathogenic variant, but it has been reported as heterozygous in one healthy control individual (Le Scouarnec et al., 2015). Additionally, the R1588X variant is observed in 8/18862 (0.04%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function through protein truncation as the last 369 amino acids of the protein are absent due to the introduction of a premature termination codon in the 3'-terminal exon. However, no downstream nonsense or truncation variants have been reported in the Human Genome Mutation Database (HGMD), and the vast majority of pathogenic variants reported in SCN10A are missense substitutions (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Ambry Genetics | RCV002341534 | SCV002635622 | likely benign | Cardiovascular phenotype | 2021-06-30 | 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. |