Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186204 | SCV000239230 | likely pathogenic | not provided | 2014-10-07 | criteria provided, single submitter | clinical testing | p.Phe101Cys (TTT>TGT): c.302 T>G in exon 3 of the SUCLG1 gene (NM_003849.3) A F101C variant that is likely pathogenic was identified in the SUCLG1 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The F101C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). |
Labcorp Genetics |
RCV001852423 | SCV002277993 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2021-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with cysteine at codon 101 of the SUCLG1 protein (p.Phe101Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is present in population databases (rs773748583, ExAC 0.001%). 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: 203979). 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 disruptive. 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. |