Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000654837 | SCV000776739 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2018-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 186 of the GJB1 protein (p.Glu186Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Charcot-Marie-Tooth disease, type IX (PMID: 8266101, 12542510, 27844031, 22243284, 11571214). ClinVar contains an entry for this variant (Variation ID: 21086). Experimental studies have shown that this missense change disrupts the formation of functional GJB1/connexin-32 gap junction channels (PMID: 9364054, 7946361, 10848620, 27844031). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000020176 | SCV000040507 | pathologic | X-linked hereditary motor and sensory neuropathy | 2010-04-15 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789812 | SCV000929196 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |