Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001240613 | SCV001413578 | uncertain significance | Long QT syndrome | 2020-01-27 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tyrosine at codon 1137 of the KCNH2 protein (p.Ser1137Tyr). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tyrosine. |
Ambry Genetics | RCV002451585 | SCV002614373 | uncertain significance | Cardiovascular phenotype | 2020-02-27 | criteria provided, single submitter | clinical testing | The p.S1137Y variant (also known as c.3410C>A), located in coding exon 15 of the KCNH2 gene, results from a C to A substitution at nucleotide position 3410. The serine at codon 1137 is replaced by tyrosine, an amino acid with dissimilar properties, and is located in the C-terminal region of the protein. This amino acid position is highly 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, |
RCV003591848 | SCV004357528 | uncertain significance | Cardiac arrhythmia | 2021-08-31 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with tyrosine at codon 1137 of the KCNH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 not been identified 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. |