ClinVar Miner

Submissions for variant NC_012920.1(MT-ND1):m.3697G>A

dbSNP: rs199476122
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Total submissions: 8
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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 RCV002221474 SCV002498785 likely pathogenic Mitochondrial disease 2022-03-24 reviewed by expert panel curation The m.3697G>A (p.G131S) variant in MT-ND1 has been reported in at least 14 individuals with primary mitochondrial disease from 8 families. Affected individuals had onset ranging from the first week of life to adulthood; and with features variably consistent with Leigh syndrome, MELAS, and LHON (PS4_moderate; PMIDs: 31996177, 30623604, 28429146, 24830958, 18977334, 17562939, 15466014). There are no reports of de novo occurrence of this variant. This variant segregated with disease in multiple affected members in multiple families and several healthy family members had lower to undetectable levels of the variant (PP1_moderate; PMIDs: 24830958, 17562939, 16969869, 15466014). This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). Functional studies supported the deleterious impact of this variant (PS3_supporting; PMID: 15466014). 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 March 22, 2022. Mitochondrial DNA-specific ACMG/AMP criteria applied: PS3_supporting, PS4_moderate, PM2_supporting, PP1_moderate.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000010385 SCV000996723 pathogenic MELAS syndrome 2019-10-17 criteria provided, single submitter clinical testing The NC_012920.1:m.3697G>A (YP_003024026.1:p.Gly131Ser) variant in MTND1 gene is interpretated to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PS1, PM8, PM9, PM10
Mendelics RCV000056168 SCV002517665 pathogenic Leber optic atrophy 2022-05-04 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV003298030 SCV004009684 likely pathogenic Migraine; Dystonic disorder; Seizure; Hypertonia; Ventriculomegaly; Developmental regression; Attention deficit hyperactivity disorder 2021-08-18 criteria provided, single submitter research
OMIM RCV000010385 SCV000030611 pathogenic MELAS syndrome 2007-06-01 no assertion criteria provided literature only
OMIM RCV000010386 SCV000030612 pathogenic Leber optic atrophy and dystonia 2007-06-01 no assertion criteria provided literature only
GeneReviews RCV000056168 SCV000087255 not provided Leber optic atrophy no assertion provided literature only
GeneReviews RCV000010385 SCV004042630 not provided MELAS syndrome no assertion provided literature only

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