Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000494941 | SCV002037590 | pathogenic | Mitochondrial disease | 2021-10-26 | reviewed by expert panel | curation | The m.13513G>A (p. D393N) variant in MT-ND5 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant has been reported in >16 individuals with primary mitochondrial disease with onset typically in childhood with some reports of onset in adolescence who had features variably consistent with Leigh syndrome, MELAS and MELAS-like, and/or mitochondrial encephalopathy (PS4; PMID: 25681084; PMID: 27344355; PMID: 30128709; PMID: 12624137; PMID: 14520659; PMID: 17400793; PMID: 18495510). This variant has been identified as a de novo occurrence in at least 5 probands with primary mitochondrial disease (PM6_strong; PMID: 27344355; PMID: 17400793; PMID: 18495510). This variant heteroplasmy level segregated with severity in 6 families where healthy mothers were found to have the variant at low heteroplasmy levels (PP1_moderate; PMID: 25681084; PMID: 12624137; PMID: 14520659). Another variant at this amino acid position leading to a different amino acid change is classified as pathogenic by mitomap.org and ClinVar – m.13514A>G (p.D393G; PM5). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.97 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). In summary, this variant meets criteria to be classified as pathogenic for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: PS4, PM6_strong, PM5, PP1_moderate, PP3). |
Center for Pediatric Genomic Medicine, |
RCV000224472 | SCV000281330 | pathogenic | not provided | 2015-07-28 | criteria provided, single submitter | clinical testing | |
Wong Mito Lab, |
RCV000144016 | SCV000997986 | pathogenic | Leigh syndrome | 2019-10-17 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.13513G>A (YP_003024036.1:p.Asp393Asn) variant in MTND5 gene is interpretated to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PS1, PS3 |
Institute of Medical Genetics and Applied Genomics, |
RCV000224472 | SCV001446569 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000494941 | SCV001949987 | pathogenic | Mitochondrial disease | 2021-08-04 | criteria provided, single submitter | clinical testing | This variant was identified as heteroplasmic (40%) |
Institute for Medical Genetics and Human Genetics, |
RCV000144016 | SCV002574885 | pathogenic | Leigh syndrome | 2022-09-22 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000144016 | SCV002580352 | pathogenic | Leigh syndrome | 2021-10-05 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000010345 | SCV000030571 | pathogenic | MELAS syndrome | 2008-03-01 | no assertion criteria provided | literature only | |
OMIM | RCV000010346 | SCV000030572 | pathogenic | Leigh syndrome due to mitochondrial complex I deficiency | 2008-03-01 | no assertion criteria provided | literature only | |
Gene |
RCV000144016 | SCV000188908 | not provided | Leigh syndrome | no assertion provided | literature only | ||
Wellcome Centre for Mitochondrial Research, |
RCV000494941 | SCV000577892 | pathogenic | Mitochondrial disease | 2017-05-22 | no assertion criteria provided | clinical testing | |
Gene |
RCV000010345 | SCV004042635 | not provided | MELAS syndrome | no assertion provided | literature only |