Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002225206 | SCV002503766 | uncertain significance | Charcot-Marie-Tooth disease type 4J | 2023-03-30 | criteria provided, single submitter | clinical testing | This sequence change is predicted to replace tyrosine with histidine at codon 134 of the FIG4 protein (p.(Tyr134His)). The tyrosine residue is evolutionarily conserved (100 vertebrates, UCSC), and is located in the SacI homology domain. There is a moderate physicochemical difference between tyrosine and histidine. The variant is absent in a large population cohort (PM2; gnomAD v2.1 and v3.0), and has been not been reported in the relevant medical literature or databases. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (PP3; 4/6 algorithms). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2, PP3. |