Submissions for variant NM_002437.5(MPV17):c.278A>C (p.Gln93Pro)

dbSNP: rs200938111

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
SIB Swiss Institute of Bioinformatics	RCV000855704	SCV000998870	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, PP1, PM3, PM1-supporting, PS3-supporting.
GeneDx	RCV002272375	SCV002558127	pathogenic	not provided	2019-11-13	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (gnomAD); The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29282788, 24321534, 21996136, 23714749, 22106832, 24894789, 28776642, 34426522)
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV000855704	SCV002574955	likely pathogenic	Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)	2022-09-16	criteria provided, single submitter	clinical testing
Invitae	RCV002272375	SCV004292106	pathogenic	not provided	2023-04-19	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 694362). This missense change has been observed in individuals with mitochondrial DNA depletion syndrome (PMID: 23714749, 28776642). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 93 of the MPV17 protein (p.Gln93Pro).
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000855704	SCV001469169	likely pathogenic	Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)	2020-02-05	no assertion criteria provided	clinical testing
GeneReviews	RCV000855704	SCV002567996	not provided	Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)		no assertion provided	literature only