Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701335 | SCV000830132 | pathogenic | Charcot-Marie-Tooth disease, type I | 2018-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 381 of the EGR2 protein (p.Arg381His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with Charcot-Marie-Tooth (CMT) (PMID: 12471219) and in several individuals affected with CMT1 (PMID: 22765307, 25720245, 10762521). ClinVar contains an entry for this variant (Variation ID: 41008). Experimental studies have shown that this missense change does not retain any transactivation capability (PMID: 12609493). A different missense substitution at this codon (p.Arg381Cys) has been reported in several individuals affected with CMT1 (PMID: 11239949, 20513111). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000033901 | SCV000057815 | pathologic | Charcot-Marie-Tooth disease, demyelinating, type 1d | 2012-10-18 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Inherited Neuropathy Consortium | RCV000789745 | SCV000929123 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
Genesis Genome Database | RCV000789745 | SCV000999523 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |