MITOMAP: Reported Mitochondrial DNA Base Substitution Diseases: Coding and Control Region Point Mutations

Last Edited: Dec 13, 2024

The GB frequency data in Mitomap is derived from 61124 GenBank sequences with size greater than 15.4kbp and 80432 Control Region sequences with size 0.4-1.6kbp. These sequences have been pre-loaded into Mitomaster and represent almost all haplogroups known to date. We will be updating and refining this set of sequences on a regular basis. As a caveat, please note that GenBank sequences may not be of equal quality (Yao, et al, 2009), that some of these sequences are from individuals with past, current or future disease, and that this portion of our data set has not been hand-curated by Mitomap.

For more details about the current GenBank sequence set, please see http://www.mitomap.org/MITOMAP/GBFreqInfo

* FL: full length sequences, CR: control reqion sequences

^◊ New: As a member of the mtDNA Variant Curation Expert Panel for ClinGen, we are adding the calculated ClinGen pathogenicity ratings after VCEP curation. This will be shown in brackets in the Mitomap Status column, for example, "Reported [VUS^◊]", "Cfrm [LP^◊]", etc. The following abbreviations are used: B, Benign; LB, Likely Benign; VUS, Variant of Uncertain Significance; LP, Likely Pathogenic; P Pathogenic. The criteria used in the ClinGen curations may be found in McCormick et al, 2020, DOI: 10.1002/humu.24107. Note that the ClinGen scoring is quite stringent and gives fewer points than Mitomap does for many types of evidence, e.g., cybrid & other functional studies, in-silico tools, absence in large databases, heteroplasmy, de-novo requirements, and case numbers.

Notes:

LHON	Leber Hereditary Optic Neuropathy	MM	Mitochondrial Myopathy
AD	Alzeimer's Disease	LIMM	Lethal Infantile Mitochondrial Myopathy
ADPD	Alzeimer's Disease and Parkinsons's Disease	MMC	Maternal Myopathy and Cardiomyopathy
NARP	Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa; alternate phenotype at this locus is reported as Leigh Disease	FICP	Fatal Infantile Cardiomyopathy Plus, a MELAS-associated cardiomyopathy
MELAS	Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes	LDYT	Leber's hereditary optic neuropathy and DYsTonia
MERRF	Myoclonic Epilepsy and Ragged Red Muscle Fibers	MHCM	Maternally inherited Hypertrophic CardioMyopathy
CPEO	Chronic Progressive External Ophthalmoplegia	KSS	Kearns Sayre Syndrome
DM	Diabetes Mellitus	DMDF	Diabetes Mellitus + DeaFness
CIPO	Chronic Intestinal Pseudoobstruction with myopathy and Ophthalmoplegia	DEAF	Maternally inherited DEAFness or aminoglycoside-induced DEAFness
PEM	Progressive encephalopathy	SNHL	SensoriNeural Hearing Loss

• Homoplasmy = pure mutant mtDNAs.
• Heteroplasmy = mixture of mutant and normal mtDNAs.
• nd = not determined.
• "Reported" status indicates that one or more publications have considered the mutation as possibly pathologic. This is not an assignment of pathogenicity by MITOMAP but is a report of literature. Previously, mutations with this status were termed "Prov" (provisional).
• "Cfrm"(confirmed) status indicates that at least two or more independent laboratories have published reports on the pathogenicity of a specific mutation. These mutations are generally accepted by the mitochondrial research community as being pathogenic. A status of "Cfrm" is not an assignment of pathogenicity by MITOMAP but is a report of published literature. Researchers and clinicians are cautioned that additional data and/or analysis may still be necessary to confirm the pathological significance of some of these mutations.
• "P.M." (point mutation / polymorphism) status indicates that some published reports have determined the mutation to be a non-pathogenic polymorphism.