ClinVar Miner

Submissions for variant m.12706T>C

dbSNP: rs267606893
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Total submissions: 5
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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 RCV002260591 SCV002540745 likely pathogenic Mitochondrial disease 2022-06-30 reviewed by expert panel curation The m.12706T>C (p.F124L) variant in MT-ND5 has been reported in at least seven unrelated individuals with primary mitochondrial disease and features including Leigh syndrome, MELAS and MELAS-like, and ophthalmoplegia (PS4_moderate; PMIDs: 34200828, 17317336, 21364701, 23847141, 14684687, 11938446). There is one report of a de novo occurrence of this variant (PS2_moderate, PMID: 17317336). 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 0.9 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). There are no cybrid studies, single fiber studies, or other functional assays reported. 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 Mitochondrial Disease Variant Curation Expert Panel on April 11, 2022. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PS4_moderate, PS2_moderate, PM2_supporting, PP3.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000144015 SCV000997893 likely pathogenic Leigh syndrome 2019-10-17 criteria provided, single submitter clinical testing The NC_012920.1:m.12706T>C (YP_003024036.1:p.Phe124Leu) variant in MTND5 gene is interpretated to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PM9, PM10, PP4, PP6, PP7
Mendelics RCV002247308 SCV002517674 pathogenic Leber optic atrophy 2022-05-04 criteria provided, single submitter clinical testing
OMIM RCV000010338 SCV000030564 pathogenic Leigh syndrome due to mitochondrial complex I deficiency 2002-02-01 no assertion criteria provided literature only
GeneReviews RCV000144015 SCV000188907 not provided Leigh syndrome no assertion provided literature only

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