ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.244T>C (p.Tyr82His) (rs281865124)

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Total submissions: 3
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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.
GeneReviews 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

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