ClinVar Miner

Submissions for variant NM_000399.5(EGR2):c.1142G>A (p.Arg381His) (rs281865137)

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Total submissions: 4
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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.
GeneReviews 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

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