Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001190373 | SCV001357836 | uncertain significance | Cardiomyopathy | 2023-03-08 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with glycine at codon 61 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 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. |
| Gene |
RCV001773442 | SCV002003416 | uncertain significance | not provided | 2020-10-09 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 927251; Landrum et al., 2016) |
| Invitae | RCV001863018 | SCV002264836 | uncertain significance | Arrhythmogenic right ventricular dysplasia 5 | 2023-05-01 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMEM43 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 927251). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 61 of the TMEM43 protein (p.Ala61Gly). |
| Ambry Genetics | RCV002411717 | SCV002715597 | uncertain significance | Cardiovascular phenotype | 2022-07-10 | criteria provided, single submitter | clinical testing | The p.A61G variant (also known as c.182C>G), located in coding exon 3 of the TMEM43 gene, results from a C to G substitution at nucleotide position 182. The alanine at codon 61 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002491572 | SCV002792786 | uncertain significance | Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant; Auditory neuropathy, autosomal dominant 3 | 2021-10-15 | criteria provided, single submitter | clinical testing |