Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001852646 | SCV002268159 | likely pathogenic | not provided | 2022-05-07 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects TK2 function (PMID: 21937588). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 38993). This variant is also known as c.688A>G (p.T230A). This missense change has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 21937588). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs281865495, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 188 of the TK2 protein (p.Thr188Ala). |
| OMIM | RCV000239458 | SCV000196097 | pathogenic | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 | 2012-01-01 | no assertion criteria provided | literature only |