ClinVar Miner

Submissions for variant NM_000399.5(EGR2):c.1225C>T (p.Arg409Trp) (rs104894159)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001049422 SCV001213471 pathogenic Charcot-Marie-Tooth disease, type I 2020-08-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 409 of the EGR2 protein (p.Arg409Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease (CMT) and to segregate with CMT in a family (PMID: 9537424, 30481651). ClinVar contains an entry for this variant (Variation ID: 16750). This variant has been reported to affect EGR2 protein function (PMID: 10369870, 26204789, 27013732). This variant disrupts the p.Arg409 amino acid residue in EGR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26204789, Invitae). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018234 SCV000038513 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1d 2003-01-14 no assertion criteria provided literature only
GeneReviews RCV000018234 SCV000055672 pathologic Charcot-Marie-Tooth disease, demyelinating, type 1d 2012-10-18 no assertion criteria provided curation Converted during submission to Pathogenic.

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