Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000619935 | SCV000737007 | uncertain significance | Cardiovascular phenotype | 2023-09-22 | criteria provided, single submitter | clinical testing | The p.R8Q variant (also known as c.23G>A), located in coding exon 1 of the SCN5A gene, results from a G to A substitution at nucleotide position 23. The arginine at codon 8 is replaced by glutamine, an amino acid with some highly similar properties. This amino acid position is not well 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. |
| Color Diagnostics, |
RCV001841795 | SCV001354367 | uncertain significance | Cardiac arrhythmia | 2023-05-22 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 8 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/278804 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. |
| Labcorp Genetics |
RCV005091767 | SCV002176818 | uncertain significance | not provided | 2024-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 8 of the SCN5A protein (p.Arg8Gln). This variant is present in population databases (rs564261427, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of long QT syndrome (internal data). ClinVar contains an entry for this variant (Variation ID: 519065). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| All of Us Research Program, |
RCV001841795 | SCV004831896 | uncertain significance | Cardiac arrhythmia | 2024-03-05 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 8 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/278804 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. |