Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000444412 | SCV000525491 | uncertain significance | not provided | 2016-03-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ARX gene. The P215Q variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge.It was not observed in approximately 4,700 individuals of European and African American ancestry inthe NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. The P215Q variant is a non-conservative amino acid substitution, which is likely toimpact secondary protein structure as these residues differ in polarity, charge, size and/or otherproperties. However, this substitution occurs at a position that is not conserved and in silico analysispredicts this variant likely does not alter the protein structure/function. Therefore, based on thecurrently available information, it is unclear whether this variant is a pathogenic variant or a rarebenign variant. |
| Labcorp Genetics |
RCV002521693 | SCV003337175 | uncertain significance | Developmental and epileptic encephalopathy, 1; Intellectual disability, X-linked, with or without seizures, arx-related | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 215 of the ARX protein (p.Pro215Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ARX-related conditions. ClinVar contains an entry for this variant (Variation ID: 384600). 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 not expected to disrupt ARX protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |