ClinVar Miner

Submissions for variant NC_012920.1(MT-TL2):m.12278T>C

dbSNP: rs1603223646
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000851069 SCV000993303 uncertain significance MELAS syndrome 2019-07-12 criteria provided, single submitter clinical testing The NC_012920.1:m.12278T>C variant in MT-TL2 gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM7, PP6
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV003225132 SCV003921834 uncertain significance Mitochondrial disease criteria provided, single submitter clinical testing - The T at this position has high conservation (MITOMASTER). - In silico predictions for this variant are consistently pathogenic (MitoTIP, PON-tRNA). - This variant is present in the MITOMAP and gnomAD population databases at frequencies of 0.002% and 0.004%, respectively. Additional information: - This variant is heteroplasmic (83.8%). - This gene encodes a mitochondrial tRNA (Leu (CUN)). - This variant is predicted to result in a nucleotide change from T to C . - This variant is located in the D-stem of the tRNA and disrupts a Watson-Crick base pairing. - The pairing nucleotide at this position in the stem (m.12286A) has high conservation (MITOMASTER). - This variant has been previously reported as likely pathogenic in two individuals with adult-onset chronic progressive external ophthalmoplegia (CPEO). It was 40.7% heteroplasmic in the muscle sample of one of the individuals. It was 18.3% heteroplasmic in the muscle sample of the other individual, who also had a pathogenic POLG variant. (PMID: 31521625) This variant has also been previously reported as uncertain significance in ClinVar . - This variant is likely maternally inherited. It has been detected in the maternal blood sample at a low heteroplasmy level (~1.9%).
Department of Clinical Genetics, Medical University of Lodz RCV003986054 SCV004801954 likely pathogenic Diabetes-deafness syndrome maternally transmitted 2024-02-19 criteria provided, single submitter literature only

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