Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001350408 | SCV001544807 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2020-10-10 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Val84 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 9401007), 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with hereditary motor & sensory neuropathy (PMID: 23011429). ClinVar contains an entry for this variant (Variation ID: 637229). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with glycine at codon 84 of the GJB1 protein (p.Val84Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. |
| Inherited Neuropathy Consortium | RCV000789299 | SCV000928652 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |