ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.245A>G (p.Tyr82Cys) (rs1553259707)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Inherited Neuropathy Consortium RCV000789442 SCV000928798 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Institute of Human Genetics,Cologne University RCV000664225 SCV000787787 pathogenic Charcot-Marie-Tooth disease dominant intermediate 3 2018-04-25 no assertion criteria provided clinical testing
Invitae RCV000701835 SCV000830654 pathogenic Charcot-Marie-Tooth disease, type I 2018-02-26 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 82 of the MPZ protein (p.Tyr82Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Déjérine-Sottas syndrome (PMID: 9633821). This variant has also been reported in several individuals affected with Charcot-Marie-Tooth (CMT) disease type 1 (PMID: 7505151, 11835375, 12402337, 11545686, 11545686, 26310628). 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 substitution at this codon (p.Tyr82Ser, Tyr82His) have been reported in individuals affected with Charcot-Marie-Tooth disease (PMID: 16543539, 25429913). For these reasons, this variant has been classified as Pathogenic.

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