Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000695028 | SCV000823502 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2018-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 115 of the PRPS1 protein (p.Met115Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with X-linked recessive Charcot-Marie-Tooth disease-5 (CMTX5) in a family (PMID: 17701900). ClinVar contains an entry for this variant (Variation ID: 9935). Experimental studies have shown that this missense change leads to decreased enzyme activity (PMID: 17701900). A different missense substitution at this codon (p.Met115Val) has been reported in an individual affected with CMTX (PMID: 25182139). 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. |
OMIM | RCV000010613 | SCV000030839 | pathogenic | Charcot-Marie-Tooth disease, X-linked recessive, type 5 | 2007-09-01 | no assertion criteria provided | literature only | |
Gene |
RCV000010613 | SCV000040925 | pathologic | Charcot-Marie-Tooth disease, X-linked recessive, type 5 | 2008-08-26 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |