Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001322919 | SCV001513811 | uncertain significance | Alpha thalassemia-X-linked intellectual disability syndrome | 2023-12-06 | 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 781 of the ATRX protein (p.Arg781Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with alpha-thalassemia X-linked intellectual disability syndrome (PMID: 35904121). ClinVar contains an entry for this variant (Variation ID: 1022948). 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 ATRX 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 |
RCV001796443 | SCV002032608 | likely pathogenic | not provided | 2024-06-22 | criteria provided, single submitter | clinical testing | Previously reported in the hemizygous state in a male individual from a cohort of patients with a neurodevelopmental phenotype; detailed clinical information was not provided (PMID: 35904121); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 35904121) |
| Ambry Genetics | RCV002431919 | SCV002731866 | uncertain significance | Inborn genetic diseases | 2015-05-22 | criteria provided, single submitter | clinical testing | The p.R781Q variant (also known as c.2342G>A), located in coding exon 9 of the ATRX gene, results from a G to A substitution at nucleotide position 2342. The arginine at codon 781 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6498 samples with coverage at this position. This amino acid position is not well 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 variant remains unclear. |