Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000200595 | SCV000254268 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2015-03-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 55 of the GJB1 protein (p.Thr55Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant has been reported in the literature and is not present in population databases. A study which looked at the clinical differences between patients with variants in three genes implicated in Charcot-Marie-Tooth disease reported this variant, however no additional information was reported regarding segregation with disease or functional effects of this variant (PMID: 12477701). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Inherited Neuropathy Consortium | RCV000789860 | SCV000929245 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |