Description
INHERITANCE: The variant was identified in the homozygous state in a patient affected by Leigh syndrome. FREQUENCY: The variant is very rare, observed in 2 / 251,172 (0.0008%) of alleles in the gnomAD v2.1.1 reference population dataset. VARIANT TYPE: Missense variant in a gene for which missense variation is a documented mechanism of disease. IN SILICO PREDICTIONS: Multiple lines of computational evidence unanimously predict a deleterious effect on the gene or gene product. The substitution replaces a highly conserved, negatively charged residue, Aspartate, with a positively charged residue, Histidine. SOURCES: This variant has been reported in ClinVar with the following classifications: VUS (2). It has also been previously described in several publications (see PMID: 19364667, 31386302, and 31292494). Notably, these studies separately describe two additional patients with the clinical diagnosis of Leigh syndrome who were carriers of this variant either in the heterozygous state, in trans with a second pathogenic variant (PMID: 19364667), or in the homozygous state (PMID: 31386302). Taken together, we interpret this variant as likely pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | 1 | not provided | not provided | not provided |
