Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000712314 | SCV000842780 | pathogenic | not provided | 2022-02-09 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant segregates with disease in multiple families. Computational tools predict that this variant is damaging. |
| Eurofins Ntd Llc |
RCV000712314 | SCV000862602 | pathogenic | not provided | 2018-07-24 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000712314 | SCV001202706 | pathogenic | not provided | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 50 of the MPV17 protein (p.Arg50Gln). This variant is present in population databases (rs121909721, gnomAD 0.003%). This missense change has been observed in individuals with mitochondrial DNA depletion syndrome or Navajo neurohepatopathy (PMID: 16582910, 16909392, 28209105). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16160). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MPV17 function (PMID: 16582910, 30833296). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509162 | SCV002819528 | pathogenic | Mitochondrial DNA depletion syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | Variant summary: MPV17 c.149G>A (p.Arg50Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251478 control chromosomes (gnomAD). c.149G>A has been reported in the literature in multiple homozygous individuals affected with Mitochondrial DNA Depletion Syndrome (MPV17 Related disorder) and the variant segregated with the disease (examples: Spinazzola_2006 and Karadimas_2006). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence suggesting that the R50Q mutation causes protein instability and decay (Karadimas_2006). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003466861 | SCV004193739 | pathogenic | Charcot-Marie-Tooth disease, axonal, type 2EE | 2023-09-26 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000017543 | SCV000037815 | pathogenic | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) | 2006-09-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000017543 | SCV000054537 | not provided | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) | no assertion provided | literature only | ||
| Natera, |
RCV000017543 | SCV001462529 | pathogenic | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) | 2020-09-16 | no assertion criteria provided | clinical testing |