Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000680168 | SCV000807642 | pathogenic | Mitochondrial DNA depletion syndrome 9 | 2017-09-01 | criteria provided, single submitter | clinical testing | This variant has been previously reported as disease-causing and was found once in our laboratory with a missense variant [Q212R - phase not determined, but mother carried M14L and not Q212R] in a 7-year-old female with bilateral hearing loss and congenital chorea. Heterozygotes for this variant are expected to be asymptomatic carriers. |
| Labcorp Genetics |
RCV000680168 | SCV002213596 | pathogenic | Mitochondrial DNA depletion syndrome 9 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 14 of the SUCLG1 protein (p.Met14Leu). This variant is present in population databases (no rsID available, gnomAD 0.04%). This missense change has been observed in individual(s) with mitochondrial DNA depletion syndrome and/or SUCLG1-related conditions (PMID: 20453710, 27484306; Invitae). 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: 561158). 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 SUCLG1 protein function. Studies have shown that this missense change alters SUCLG1 gene expression (PMID: 27484306). This variant disrupts the p.Met14 amino acid residue in SUCLG1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21639866, 29217198, 35094435). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |