ClinVar Miner

Submissions for variant NM_139058.3(ARX):c.1615G>A (p.Ala539Thr)

dbSNP: rs2147318633
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002023895 SCV002302595 likely pathogenic Developmental and epileptic encephalopathy, 1; Intellectual disability, X-linked, with or without seizures, arx-related 2021-08-09 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala539 amino acid residue in ARX. Other variant(s) that disrupt this residue have been observed in individuals with ARX-related conditions (PMID: 28174645, Invitae), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt ARX protein function. This variant has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 539 of the ARX protein (p.Ala539Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.