ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.164C>T (p.Thr55Ile) (rs104894824)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486043 SCV000568357 pathogenic not provided 2017-02-21 criteria provided, single submitter clinical testing The T55I variant in the GJB1 gene has been previously reported several times in association with CMTX1 (Karadimas et al., 1999; Panas et al., 2001; Hahn et al., 2001). Functional studies indicate that T55I impairs protein trafficking to the cell membrane and inhibits the formation of functional gap junctions (Abrams et al., 2017; Kleopa et al., 2002). The T55I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T55I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, multiple missense variants in nearby residues and at the same residue (T55A/R) have been reported in the Human Gene Mutation Database in association with GJB1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein.
OMIM RCV000011191 SCV000031418 pathogenic Charcot-Marie-Tooth Neuropathy X Type 1 2001-11-27 no assertion criteria provided literature only
GeneReviews RCV000011191 SCV000040499 pathologic Charcot-Marie-Tooth Neuropathy X Type 1 2010-04-15 no assertion criteria provided curation Converted during submission to Pathogenic.
Inherited Neuropathy Consortium RCV000789872 SCV000929257 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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