Submissions for variant m.13513G>A

dbSNP: rs267606897

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen	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, Children's Mercy Hospital and Clinics	RCV000224472	SCV000281330	pathogenic	not provided	2015-07-28	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	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, University Hospital Tübingen	RCV000224472	SCV001446569	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	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, Charité - Universitätsmedizin Berlin	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	Juvenile myopathy, encephalopathy, lactic acidosis AND stroke	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
GeneReviews	RCV000144016	SCV000188908	not provided	Leigh syndrome		no assertion provided	literature only
Wellcome Centre for Mitochondrial Research, Newcastle University	RCV000494941	SCV000577892	pathogenic	Mitochondrial disease	2017-05-22	no assertion criteria provided	clinical testing
GeneReviews	RCV000010345	SCV004042635	not provided	Juvenile myopathy, encephalopathy, lactic acidosis AND stroke		no assertion provided	literature only