Submissions for variant NM_000530.8(MPZ):c.106A>G (p.Arg36Gly) (rs864622732)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478575	SCV000568793	likely pathogenic	not provided	2017-02-24	criteria provided, single submitter	clinical testing	The R36G variant has been reported previously in a patient and her son with progressive axonal and demyelinating sensorimotor neuropathy, respectively (Dacci et al., 2012). The R36G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R36G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, multiple missense variants in nearby residues and at the same residue (R36W) have been reported in the Human Gene Mutation Database in association with MPZ-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Inherited Neuropathy Consortium	RCV000790071	SCV000929461	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only