ClinVar

Description

Variant summary: MPV17 c.122G>A (p.Arg41Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251486 control chromosomes. c.122G>A has been reported in the literature as a homozygous genotype in multiple individuals affected with features of MPV17 related axonal sensorimotor polyneuropathy without liver and brain involvement, which is neurophysiologically similar to axonal Charcot-Marie-Tooth disease (CMT) (example, PMID: 30298599, 26437932). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function reporting significantly inhibited cell proliferation when compared to controls (example, PMID: 26437932). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.