Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000471834 | SCV000552820 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2017-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with arginine at codon 23 of the PMP22 protein (p.Thr23Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth disease, type 1A (CMT1A) and has been observed to segregate with CMT1A in a single family (PMID: 23263778, 15099592, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. |
| Athena Diagnostics Inc | RCV000518509 | SCV000614680 | uncertain significance | not specified | 2017-03-08 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000789510 | SCV000928866 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |