Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000714948 | SCV000845724 | likely pathogenic | Combined oxidative phosphorylation defect type 14 | 2018-06-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000714948 | SCV001234219 | pathogenic | Combined oxidative phosphorylation defect type 14 | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 156 of the FARS2 protein (p.Thr156Met). This variant is present in population databases (rs146988468, gnomAD 0.06%). This missense change has been observed in individual(s) with early onset epileptic encephalopathy (PMID: 27652284, 33972171). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 587677). 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 FARS2 protein function. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV003326510 | SCV004032657 | likely pathogenic | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | FARS2: PM3:Strong, PM2 |