Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000240821 | SCV001468551 | likely pathogenic | Mitochondrial complex 4 deficiency, nuclear type 12 | 2020-12-04 | criteria provided, single submitter | curation | This variant is interpreted as Likely pathogenic for Mitochondrial complex IV deficiency, nuclear type 12, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants (PM4); Well-established functional studies show a deleterious effect (PS3 downgraded to moderate). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330441 | SCV004038304 | pathogenic | Cytochrome-c oxidase deficiency disease | 2023-08-07 | criteria provided, single submitter | clinical testing | Variant summary: PET100 c.142C>T (p.Gln48X) results in a premature termination codon, predicted to cause a truncation of the encoded protein, which is a known mechanisms for disease. While this variant is not expected to result in nonsense mediated decay, it is predicted to disrupt the last 26 amino acids of the protein. The variant allele was found at a frequency of 7.3e-06 in 137842 control chromosomes (i.e., 1 heterozygote; gnomAD v2 Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.142C>T has been reported in the literature in at least one homozygous individual affected with Cytochrome-c oxidase deficiency disease (e.g., Olahova_2015). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in <10% complex IV activity in homozygous patient muscle tissue and fibroblasts (e.g., Olahova_2015). The following publication was ascertained in the context of this evaluation (PMID: 25293719). Two submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Wellcome Centre for Mitochondrial Research, |
RCV000144455 | SCV000148974 | pathogenic | Cytochrome-c oxidase deficiency disease; Congenital lactic acidosis | 2014-05-12 | no assertion criteria provided | clinical testing | |
| OMIM | RCV000240821 | SCV000299305 | pathogenic | Mitochondrial complex 4 deficiency, nuclear type 12 | 2020-10-23 | no assertion criteria provided | literature only |