ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.556G>A (p.Glu186Lys) (rs116840821)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654837 SCV000776739 pathogenic Charcot-Marie-Tooth Neuropathy X 2019-10-24 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.
GeneReviews RCV000020176 SCV000040507 pathologic Charcot-Marie-Tooth Neuropathy X Type 1 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

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