Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000691854 | SCV000819650 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2020-01-07 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val177 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 10586284, 20491857, 9856562), which suggests that this may be a clinically significant amino acid residue. 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 C15"). This variant has been reported in individual(s) with clinical features of Charcot-Marie-Tooth (CMT) disease (PMID: 24078732, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 570878). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 177 of the GJB1 protein (p.Val177Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |
| Inherited Neuropathy Consortium | RCV000789941 | SCV000929326 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |