Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001380433 | SCV001578511 | pathogenic | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2020-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 114 of the INF2 protein (p.Gly114Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of INF2-related conditionss (PMID: 24174593, 25943269, 31515790, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 637704). 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. For these reasons, this variant has been classified as Pathogenic. |
Inherited Neuropathy Consortium | RCV000789986 | SCV000929375 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |