ClinVar Miner

Submissions for variant NC_012920.1(MT-CYB):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 Juvenile myopathy, encephalopathy, lactic acidosis AND stroke 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C variant in MT-TL2 gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished).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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