Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000221861 | SCV000272407 | uncertain significance | not specified | 2015-04-13 | criteria provided, single submitter | clinical testing | The p.Ala413Ser variant in SCN5A has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction to ols and conservation analysis do not provide strong evidence for or against an i mpact the protein. In summary, the clinical significance of the p.Ala413Ser vari ant is uncertain. |
| Ambry Genetics | RCV002363077 | SCV002662654 | uncertain significance | Cardiovascular phenotype | 2022-02-01 | criteria provided, single submitter | clinical testing | The p.A413S variant (also known as c.1237G>T), located in coding exon 9 of the SCN5A gene, results from a G to T substitution at nucleotide position 1237. The alanine at codon 413 is replaced by serine, an amino acid with similar properties. This alteration has been reported in an epilepsy cohort with limited clinical details, as well as a pediatric cardiomyopathy cohort in an individual with limited clinical details and additional alterations in other cardiac-related genes (Li X et al. Ann Hum Genet, 2020 03;84:161-168; Burstein DS et al. Pediatr Res, 2021 05;89:1470-1476). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |