Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000186202 | SCV000239228 | uncertain significance | not provided | 2013-08-12 | criteria provided, single submitter | clinical testing | p.Tyr337Cys (TAC>TGC): c.1010 A>G in exon 8 of the SUCLG1 gene (NM_003849.3) A variant of unknown significance has been identified in the SUCLG1 gene. The Y337C missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. Y337C is a semi-conservative change in that both Tyrosine and Cysteine are uncharged, polar residues; however, the introduction of a Cysteine residue may impact disulfide bonding and the secondary structure of the SUCLG1 protein. This change occurs at a position in the SUCLG1 protein that is not well conserved. In-silico analyses are not consistent in their predictions of whether or not Y337C is damaging to the SUCLG1 protein. Therefore, based on the currently available information, it is unclear whether Y337C is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). |
| Labcorp Genetics |
RCV001852422 | SCV002306491 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 337 of the SUCLG1 protein (p.Tyr337Cys). This variant is present in population databases (rs767950611, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SUCLG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 203977). 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. 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. |