ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.1586_1587delinsAG (p.Arg529Gln) (rs863224454)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196497 SCV000253716 pathogenic Charcot-Marie-Tooth disease type 4 2018-12-26 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.

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