Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 |