ClinVar Miner

Submissions for variant NC_012920.1(MT-TK):m.8319A>G

dbSNP: rs1603221401
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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 RCV005415447 SCV006082471 uncertain significance Mitochondrial disease 2024-11-11 reviewed by expert panel curation The m.8319A>G variant in MT-TK has been reported in one individual with primary mitochondrial disease to date (PMID: 23463613; also likely same case reported in PMID: 31965079), in a person with Kearns Sayre syndrome (KSS) with the variant present at 87% in muscle. The variant was undetectable in blood from the healthy mother (PM6_supporting). There are no reports of additional families with this variant segregating with clinical manifestations. This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). In silico predictors are conflicting as the computational predictor MitoTIP suggests this variant is possibly pathogenic (69.6 percentile) but HmtVAR predicts it to be likely benign with a score of 0.25. There are no cybrids, single fiber studies, or other functional assays reported on this variant. 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 ClinGen Mitochondrial Disease Variant Curation Expert Panel on November 11, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PM6_supporting.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000850944 SCV000993178 likely pathogenic MELAS syndrome 2019-07-12 criteria provided, single submitter clinical testing The NC_012920.1:m.8319A>G variant in MT-TK gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM2, PM9, PP3, PP6
MGZ Medical Genetics Center RCV002290478 SCV002580749 uncertain significance Kearns-Sayre syndrome 2022-02-25 criteria provided, single submitter clinical testing

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