Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003541103 | SCV001201184 | uncertain significance | not provided | 2019-01-26 | criteria provided, single submitter | clinical testing | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with long QT-syndrome (LQTS) (PMID: 23174487). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 1781 of the SCN5A protein (p.Glu1781Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. |
Ambry Genetics | RCV002346249 | SCV002646266 | uncertain significance | Cardiovascular phenotype | 2020-06-04 | criteria provided, single submitter | clinical testing | The p.E1781G variant (also known as c.5342A>G), located in coding exon 27 of the SCN5A gene, results from an A to G substitution at nucleotide position 5342. The glutamic acid at codon 1781 is replaced by glycine, an amino acid with similar properties, and is located in the C-terminal, cytoplasmic region of the protein. This variant has been detected in a long QT syndrome cohort; however, details were limited (Mullally J et al. Heart Rhythm, 2013 Mar;10:378-82; Wilde AA et al. Circulation, 2016 Sep;134:872-82). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |