Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003065266 | SCV003454354 | uncertain significance | Long QT syndrome | 2023-04-28 | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2145897). This missense change has been observed in individual(s) with ventricular tachycardia (PMID: 29396286). This variant is present in population databases (rs760372805, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 353 of the KCNH2 protein (p.Thr353Ser). |
Color Diagnostics, |
RCV003591979 | SCV004358348 | uncertain significance | Cardiac arrhythmia | 2022-01-25 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with serine at codon 353 of the KCNH2 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 myocardial infarction and ventricular tachycardia (PMID: 29396286). This variant has been identified in 2/248146 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. |