Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498530 | SCV000589888 | pathogenic | not provided | 2019-08-29 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect; This variant is associated with the following publications: (PMID: 28589176, 29130122, 31035234, 32533790, 32939676) |
Ai |
RCV000498530 | SCV002502962 | likely pathogenic | not provided | 2020-05-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000723327 | SCV004299580 | pathogenic | Developmental and epileptic encephalopathy, 8 | 2023-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 104 of the ARHGEF9 protein (p.Arg104Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ARHGEF9-related conditions (PMID: 28589176, 32939676). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 432195). 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 ARHGEF9 protein function. For these reasons, this variant has been classified as Pathogenic. |
Biochemical Molecular Genetic Laboratory, |
RCV000723327 | SCV000854721 | likely pathogenic | Developmental and epileptic encephalopathy, 8 | 2018-07-06 | no assertion criteria provided | clinical testing |