Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003541167 | SCV001582274 | pathogenic | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Thr1620 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9521325, 10532948, 10618304, 11029409, 11123251, 11827685, 15520322). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1620 of the SCN5A protein (p.Thr1620Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of long QT syndrome (PMID: 18065446, 32383558; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 67931). 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 disruptive. Experimental studies have shown that this missense change affects SCN5A function (PMID: 18065446). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |
| Ambry Genetics | RCV004019055 | SCV004944526 | uncertain significance | Cardiovascular phenotype | 2022-09-06 | criteria provided, single submitter | clinical testing | The c.4859C>A (p.T1620K) alteration is located in exon 28 (coding exon 27) of the SCN5A gene. This alteration results from a C to A substitution at nucleotide position 4859, causing the threonine (T) at amino acid position 1620 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Cardiovascular Biomedical Research Unit, |
RCV000058714 | SCV000090234 | not provided | Conduction system disorder | no assertion provided | literature only | This variant has been reported as associated with Cardiac conduction disease in the following publications (PMID:18065446;PMID:21552533). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |