Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803773 | SCV000943659 | pathogenic | Developmental and epileptic encephalopathy, 8 | 2022-08-25 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of ARHGEF9-related condition (Invitae). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. 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: "Benign"; Align-GVGD: "Class C55"). ClinVar contains an entry for this variant (Variation ID: 648941). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 179 of the ARHGEF9 protein (p.Glu179Lys). |
| Ambry Genetics | RCV002345802 | SCV002641598 | uncertain significance | Inborn genetic diseases | 2017-10-12 | criteria provided, single submitter | clinical testing | The p.E179K variant (also known as c.535G>A), located in coding exon 4 of the ARHGEF9 gene, results from a G to A substitution at nucleotide position 535. The glutamic acid at codon 179 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Genome |
RCV003128417 | SCV003804788 | not provided | ARHGEF9-related neurodevelopmental disorder | no assertion provided | phenotyping only | Variant interpreted as Likely pathogenic and reported on 03-31-2022 by Children's Hospital of Philadelphia. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Philip Payne PhD, FACMI from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. |