Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 | |
Gene |
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 |