Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001180241 | SCV001345120 | uncertain significance | Cardiomyopathy | 2023-06-28 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with isoleucine at codon 190 of the TMEM43 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 TMEM43-related disorders in the literature. This variant has been identified in 1/251342 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. |
| Invitae | RCV002558948 | SCV003504149 | uncertain significance | Arrhythmogenic right ventricular dysplasia 5 | 2022-04-11 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 190 of the TMEM43 protein (p.Phe190Ile). This variant is present in population databases (rs768718054, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. ClinVar contains an entry for this variant (Variation ID: 921092). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Gene |
RCV003225153 | SCV003921592 | uncertain significance | not provided | 2022-10-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |