Submissions for variant NM_000530.8(MPZ):c.337G>T (p.Val113Phe) (rs281865126)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657923	SCV000779690	uncertain significance	not provided	2018-05-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the MPZ gene. The V113F variant has been previously reported in an individual with demyelinating and axonal peripheral neuropathy, pes cavus, and pupillary light-near dissociation (Bienfait et al., 2002). However, this individual was also found to carry another variant (H81Y) on the same allele and parental studies were not performed. The V113F variant is not observed in large population cohorts (Lek et al., 2016). The V113F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with MPZ-related disorders (Stenson et al., 2014). However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
GeneReviews	RCV000033917	SCV000057833	pathogenic	Charcot-Marie-Tooth disease, demyelinating, type 1b	2015-03-26	no assertion criteria provided	literature only
Inherited Neuropathy Consortium	RCV000789425	SCV000928780	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only