ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.89T>C (p.Ile30Thr) (rs281865121)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001051613 SCV001215779 likely pathogenic Charcot-Marie-Tooth disease, type I 2020-02-12 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 30 of the MPZ protein (p.Ile30Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease (PMID: 17143884, Invitae). ClinVar contains an entry for this variant (Variation ID: 41014). This variant has been reported to affect MPZ protein function (PMID: 20461396). This variant disrupts the p.Ile30 amino acid residue in MPZ. Other variant(s) that disrupt this residue (p.Ile30Met) have been observed in individuals with MPZ-related conditions (PMID: 7694726), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews RCV000033911 SCV000057827 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-03-26 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789434 SCV000928789 uncertain significance Dejerine-Sottas disease no assertion criteria provided literature only

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