Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000283566 | SCV000432160 | uncertain significance | Mitochondrial DNA depletion syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000329205 | SCV000432161 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000329205 | SCV001396036 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2022-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 34 of the SUCLG1 protein (p.Pro34Leu). This variant is present in population databases (rs149809280, gnomAD 0.07%). 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: 337160). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003401359 | SCV004122812 | uncertain significance | not specified | 2023-10-12 | criteria provided, single submitter | clinical testing | Variant summary: SUCLG1 c.101C>T (p.Pro34Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-05 in 214042 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SUCLG1 causing Mitochondrial DNA Depletion Syndrome 9 (8.4e-05 vs ND), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.101C>T in individuals affected with Mitochondrial DNA Depletion Syndrome 9 and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |