ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.89T>C (p.Ile30Thr) (rs104894817)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001061206 SCV001225940 pathogenic Charcot-Marie-Tooth Neuropathy X 2019-11-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 30 of the GJB1 protein (p.Ile30Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 9818870, Invitae). ClinVar contains an entry for this variant (Variation ID: 637215). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB1 protein function. This variant disrupts the p.Ile30 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 7477983, 27549087), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789282 SCV000928635 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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