ClinVar Miner

Submissions for variant NM_002437.5(MPV17):c.461G>T (p.Arg154Met)

dbSNP: rs886044113
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485587 SCV000565177 likely pathogenic not provided 2014-12-19 criteria provided, single submitter clinical testing A novel R154M (c.461 G>T) variant that is likely pathogenic was identified in the MPV17 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The R154M missense change is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (A162D) has been reported in the Human Gene Mutation Database in association with mitochondrial DNA depletion syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, several in-silico splice prediction models predict that the c.461 G>T nucleotide substitution, responsible for R154M, damages the natural splice donor site for exon 7 which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.461 G>T sequence change in this individual is unknown. Therefore, R154M (c.461 G>T) is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000625516 SCV000746012 likely pathogenic Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) 2017-12-01 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000625516 SCV000998886 likely pathogenic Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) 2019-08-13 criteria provided, single submitter curation This variant is interpreted as a Likely pathogenic for Mitochondrial DNA depletion syndrome 6, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PP3, PM3-strong.
Baylor Genetics RCV003470524 SCV004193757 likely pathogenic Charcot-Marie-Tooth disease, axonal, type 2EE 2023-04-08 criteria provided, single submitter clinical testing

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.