Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002260696 | SCV002540741 | uncertain significance | Mitochondrial disease | 2022-06-30 | reviewed by expert panel | curation | The m.13379A>C (p.H348P) variant in MT-ND5 has been reported in one individual from one family (PMID: 17003408), in a male with LHON. The variant was present at homoplasmy in blood and haplogroup was M1. Although it is reported in this paper that this proband had a family history of poor vision, no details are provided. This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.80 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). There are no functional studies 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 Mitochondrial Disease Variant Curation Expert Panel on May 3, 2022. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PP3. |