Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000196497 | SCV000253716 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2019-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 529 of the SH3TC2 protein (p.Arg529Gln). The arginine residue highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs80338923, ExAC <0.01%). This variant has been reported in the literature in several individuals affected with Charcot-Marie-Tooth disease type 4C (PMID: 19744956, 23281072, 14574644, 21840889, 28555600). ClinVar contains an entry for this variant (Variation ID: 21600). Experimental studies have shown that SH3TC2 protein with this missense change is decreased or absent from the plasma membrane when compared with wild-type SH3TC2 protein (PMID: 19744956). Additional studies have shown that SH3TC2 protein with this variant fails to promote ERBB2 internalization (PMID: 23553667), which is suggested to disrupt proper myelination. For these reasons, this variant has been classified as Pathogenic. |