ClinVar Miner

Submissions for variant NC_012920.1(MT-CYB):m.5538G>A

dbSNP: rs1603220012
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen RCV001796794 SCV002037591 uncertain significance Mitochondrial disease 2021-10-26 reviewed by expert panel curation The m.5538G>A variant in MT-TW was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant has been reported in three affected individuals in two families (PMID: 20708751, PMID: 29043143), however haplogroups were not provided as necessary to apply PS4_supporting. No instances of de novo inheritance have been reported. There has been only one report of multiple family members with this variant and only mother and proband were reported although variant heteroplasmy load did correlate with symptoms in proband and mother (PMID: 20708751). This variant is absent in the GenBank data set and gnomAD v3.1.2 (PM2_supporting). The computational predictor MitoTIP suggests this variant impacts the function of this tRNA with a score of 76.70%, as does HmtVar with a score of 0.75 (PP3). In summary, there is not sufficient evidence to characterize this variant as pathogenic or benign, therefore it is characterized as a variant of uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. While this variant is reported in three affected individuals, absent from population databases, and predicted to effect tRNA function, additional evidence of pathogenicity is not yet present. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: PM2_supporting, PP3.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000850783 SCV000993016 pathogenic Juvenile myopathy, encephalopathy, lactic acidosis AND stroke 2019-07-12 criteria provided, single submitter clinical testing The NC_012920.1:m.5538G>A variant in MT-TW gene is interpreted to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PS3, PM7, PM8, PM9, PP6

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.