Submissions for variant NM_000530.8(MPZ):c.244T>C (p.Tyr82His)

dbSNP: rs281865124

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000693764	SCV000821645	pathogenic	Charcot-Marie-Tooth disease, type I	2023-01-24	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 82 of the MPZ protein (p.Tyr82His). This missense change has been observed in individual(s) with late onset axonal Charcot-Marie-Tooth disease (PMID: 16543539). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr82 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7505151, 9633821, 12402337, 25429913). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 41017).
CeGaT Center for Human Genetics Tuebingen	RCV001699102	SCV002585165	pathogenic	not provided	2022-08-01	criteria provided, single submitter	clinical testing	MPZ: PP1:Strong, PM2, PM5, PS4:Moderate
Institute of Human Genetics, University Hospital of Duesseldorf	RCV003335061	SCV004046809	likely pathogenic	Charcot-Marie-Tooth disease dominant intermediate D		criteria provided, single submitter	not provided
Institute of Human Genetics, University Hospital of Duesseldorf	RCV003444056	SCV004171178	likely pathogenic	Charcot-Marie-Tooth disease type 2I		criteria provided, single submitter	not provided
Human Genetics Bochum, Ruhr University Bochum	RCV003886367	SCV004704563	likely pathogenic	See cases	2023-10-23	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PS4_MOD, PM5, PM2_SUP, PP1, PP3
GeneReviews	RCV000033914	SCV000057830	not provided	Charcot-Marie-Tooth disease type 1B		no assertion provided	literature only
Inherited Neuropathy Consortium	RCV000789426	SCV000928781	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only
Clinical Genetics, Academic Medical Center	RCV001699102	SCV001918670	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699102	SCV001955908	likely pathogenic	not provided		no assertion criteria provided	clinical testing