ClinVar Miner

Submissions for variant NC_012920.1(MT-CYB):m.15242G>A

dbSNP: rs207459999
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen RCV004691092 SCV005187327 likely pathogenic Mitochondrial disease 2024-01-08 reviewed by expert panel curation The m.15242G>A (p.Gly166Ter) variant in MT-CYB has been reported in one individual with primary mitochondrial disease. This individual had exercise intolerance, lactic acidosis, encephalomyopathy, hallucinations, depression, memory loss, and seizures. The variant was present at 87-92% heteroplasmy in muscle, 0.7% in blood, and 4-14% in hair roots (PMID:11047755). This variant was also seen in her unaffected sister (<0.2% in blood) and was undetectable in blood from her healthy mother, however this cannot be considered evidence for segregation nor de novo occurrence as the variant was detected at very low levels in the proband’s blood. This variant causes a premature stop in the MT-CYB gene (PVS1_strong). This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). There are no in silico predictors for this type of variant in mitochondrial DNA. Single fiber testing showed higher levels of the variant in ragged red fibers (89±8%) than in non-ragged red fibers (66±26%) p<0.0001 (PS3_supporting, PMID: 11047755). In summary, this variant meets criteria to be classified as likely pathogenic 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 January 8, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PVS1_strong, PS3_supporting.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000855252 SCV000998302 pathogenic Leigh syndrome 2019-10-17 criteria provided, single submitter clinical testing The NC_012920.1:m.15242G>A (YP_003024038.1:p.Gly166Ter) variant in MTCYB gene is interpretated to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PS3, PS6, PM8, PM9
OMIM RCV000010318 SCV000030543 pathogenic Mitochondrial encephalomyopathy 2000-12-01 no assertion criteria provided literature only

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