ClinVar Miner

Submissions for variant m.3700G>A

dbSNP: rs397515508
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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 RCV002221484 SCV002498786 uncertain significance Mitochondrial disease 2022-03-24 reviewed by expert panel curation The m.3700G>A (p.A132T) variant in MT-ND1 has been reported in 3 individuals with primary mitochondrial disease who had features consistent with Leigh syndrome (1/3) and LHON (2/3; PS4_supporting; PMIDs: 30128709, 22879922, 12150954). There are no reports of de novo occurrences of this variant. There are no reports of testing in family members to date to consider for segregation. There are 3 occurrences of this variant in GenBank dataset, however 2/3 are from individuals with known mitochondrial disease. This variant is absent in gnomAD v3.1.2 and in Helix dataset therefore this variant is present at <1/50,000 healthy individuals (PM2_supporting). There are no functional studies reported. The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.53 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). In summary, this variant meets criteria to be classified as uncertain significance 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: PS4_supporting, PM2_supporting, PP3.
GeneReviews RCV000055708 SCV000086634 not provided Leber optic atrophy no assertion provided literature only This mitochondrial DNA variant affects function. It hase been identified in at least two independent LHON pedigrees and segregates with affected disease status.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000415448 SCV000492640 pathogenic Visual loss; Abnormal electroretinogram; Optic neuropathy 2016-03-21 no assertion criteria provided clinical testing

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