Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004791208 | SCV005407792 | uncertain significance | Mitochondrial disease | 2023-08-14 | reviewed by expert panel | curation | The m.14596A>T (p.I26M) variant in MT-ND6 has been reported in one family with primary mitochondrial disease to date (PMID: 8644732). Affected individuals had clinical features consistent with Leber Hereditary Optic Neuropathy (LHON) and/or spastic dystonia. Of note, another variant was seen in this family (m. 11696G>A), however this is present in healthy population databases and likely haplogroup-associated. The m.14596A>T variant was present at homoplasmy in affected individuals. As all tested individuals were homoplasmic for the variant, segregation evidence could not be considered. There are no additional families reported with de novo occurrences to our knowledge. This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). The computation predictor APOGEE predicts this variant to be deleterious (score 0.95 in APOGEE1 and 0.86 in APOGEE2; PP3). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on August 14, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PP3. |
OMIM | RCV000010329 | SCV000030555 | pathogenic | Leber optic atrophy and dystonia | 1996-04-01 | no assertion criteria provided | literature only | |
Gene |
RCV000055704 | SCV000086629 | not provided | Leber optic atrophy | no assertion provided | literature only |