Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821192 | SCV000961941 | uncertain significance | Developmental and epileptic encephalopathy, 1; Intellectual disability, X-linked, with or without seizures, arx-related | 2023-12-11 | 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 185 of the ARX protein (p.Pro185Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 663334). 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. |
Gene |
RCV001585760 | SCV001812144 | likely benign | not provided | 2020-02-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345895 | SCV002649429 | uncertain significance | Inborn genetic diseases | 2020-01-07 | criteria provided, single submitter | clinical testing | The p.P185Q variant (also known as c.554C>A), located in coding exon 2 of the ARX gene, results from a C to A substitution at nucleotide position 554. The proline at codon 185 is replaced by glutamine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |