Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693764 | SCV000821645 | pathogenic | Charcot-Marie-Tooth disease, type I | 2018-04-17 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with histidine at codon 82 of the MPZ protein (p.Tyr82His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with late onset axonal Charcot-Marie-Tooth disease in 2 families (PMID: 16543539). ClinVar contains an entry for this variant (Variation ID: 41017). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Different missense substitutions at this codon (p.Tyr82Cys, p.Tyr82Ser) have been reported in individuals affected with Charcot-Marie-Tooth disease (PMID: 9633821, 7505151, 12402337, 25429913). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000033914 | SCV000057830 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 2015-03-26 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium | RCV000789426 | SCV000928781 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |