Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001228020 | SCV001400401 | pathogenic | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E | 2019-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tryptophan at codon 104 of the INF2 protein (p.Cys104Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis in a family (PMID: 22187985). This variant has also been observed in individuals with clinical features of Charcot-Marie-Tooth disease (PMID: 29653220, Invitae). ClinVar contains an entry for this variant (Variation ID: 30866). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000023851 | SCV000045142 | pathogenic | Charcot-Marie-Tooth disease, dominant intermediate E | 2011-12-22 | no assertion criteria provided | literature only |