Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001235260 | SCV001407939 | uncertain significance | Brugada syndrome | 2019-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with isoleucine at codon 1628 of the SCN10A protein (p.Ser1628Ile). The serine residue is weakly conserved and there is a large physicochemical difference between serine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Ambry Genetics | RCV004033276 | SCV003727904 | uncertain significance | Cardiovascular phenotype | 2024-06-30 | criteria provided, single submitter | clinical testing | The p.S1628I variant (also known as c.4883G>T), located in coding exon 27 of the SCN10A gene, results from a G to T substitution at nucleotide position 4883. The serine at codon 1628 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Mayo Clinic Laboratories, |
RCV003481009 | SCV004226078 | uncertain significance | not provided | 2022-05-13 | criteria provided, single submitter | clinical testing | PM2 |