Submissions for variant NM_000530.8(MPZ):c.186C>G (p.Ile62Met) (rs121913605)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000799870	SCV000939552	uncertain significance	Charcot-Marie-Tooth disease, type I	2018-07-13	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with methionine at codon 62 of the MPZ protein (p.Ile62Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs121913605, ExAC 0.003%). This variant has been observed in an individual affected with Charcot-Marie-Tooth disease (PMID: 14638973). ClinVar contains an entry for this variant (Variation ID: 14194). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the p.Ile62 amino acid residue in MPZ have been observed in affected individuals (PMID: 10214757, 11935267). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV001196641	SCV001367261	uncertain significance	Myopathy	2019-08-27	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this varinat's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2. This variant was detected in hemizygous state.
OMIM	RCV000015258	SCV000035517	pathogenic	Charcot-Marie-Tooth disease type 2I	2003-11-25	no assertion criteria provided	literature only

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