Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002525576 | SCV000548691 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2017-01-19 | criteria provided, single submitter | clinical testing | This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with catecholaminergic polymorphic ventricular tachycardia (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CASQ2-related disease. This sequence change replaces isoleucine with serine at codon 149 of the CASQ2 protein (p.Ile149Ser). The isoleucine residue is moderately conserved and there is a large physicochemical difference between isoleucine and serine. |
| Ambry Genetics | RCV004022703 | SCV005017053 | uncertain significance | Cardiovascular phenotype | 2023-10-13 | criteria provided, single submitter | clinical testing | The p.I149S variant (also known as c.446T>G), located in coding exon 4 of the CASQ2 gene, results from a T to G substitution at nucleotide position 446. The isoleucine at codon 149 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is 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. |