Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001224751 | SCV001396970 | pathogenic | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2019-09-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu57 amino acid residue in INF2. Other variant(s) that disrupt this residue have been observed in individuals with INF2-related conditions (PMID: 25676889), 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed to be de novo in individuals with clinical features of Charcot-Marie-Tooth disease (PMID: 22187985, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 57 of the INF2 protein (p.Leu57Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |
| Inherited Neuropathy Consortium | RCV000789982 | SCV000929371 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |