Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000525236 | SCV000652128 | likely pathogenic | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2023-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 133 of the INF2 protein (p.Asp133Asn). This variant is present in population databases (rs774135330, gnomAD 0.0009%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 472865). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on INF2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Mayo Clinic Laboratories, |
RCV001508742 | SCV001715088 | uncertain significance | not provided | 2019-12-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001508742 | SCV004012762 | uncertain significance | not provided | 2025-03-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22965130) |