Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001187101 | SCV001353765 | uncertain significance | Cardiomyopathy | 2020-01-07 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with tyrosine at codon 305 of the TMEM43 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 6/251454 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 | RCV003600405 | SCV004554839 | uncertain significance | Arrhythmogenic right ventricular dysplasia 5 | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs777277570, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 305 of the TMEM43 protein (p.Ser305Tyr). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 925267). |