Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001228020 | SCV001400401 | pathogenic | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2022-01-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys104 amino acid residue in INF2. Other variant(s) that disrupt this residue have been observed in individuals with INF2-related conditions (PMID: 22187985, 30373780), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt INF2 protein function. ClinVar contains an entry for this variant (Variation ID: 30866). This missense change has been observed in individuals with clinical features of Charcot-Marie-Tooth disease and Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis (PMID: 22187985, 29653220; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 104 of the INF2 protein (p.Cys104Trp). |
| OMIM | RCV000023851 | SCV000045142 | pathogenic | Charcot-Marie-Tooth disease dominant intermediate E | 2011-12-22 | no assertion criteria provided | literature only |