Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002326606 | SCV002609099 | uncertain significance | Cardiovascular phenotype | 2020-02-11 | criteria provided, single submitter | clinical testing | The p.D1114E variant (also known as c.3342C>A), located in coding exon 17 of the SCN5A gene, results from a C to A substitution at nucleotide position 3342. The aspartic acid at codon 1114 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV004005623 | SCV004831697 | uncertain significance | Cardiac arrhythmia | 2023-07-10 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 1114 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with long QT syndrome (PMID: 26669661) and in another individual affected with hypertrophic cardiomyopathy, who also carried a pathogenic variant in the MYH7 gene that could explain the observed phenotype (PMID: 30847666). This variant has been identified in 1/239156 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |