Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001261411 | SCV001438337 | uncertain significance | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 | 2020-10-04 | criteria provided, single submitter | clinical testing | ACMG criteria used for classification: PM1, PM2, PP2 |
Invitae | RCV001880019 | SCV002162957 | uncertain significance | not provided | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 522 of the TWNK protein (p.Met522Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TWNK-related conditions. ClinVar contains an entry for this variant (Variation ID: 981929). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TWNK 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. |