ClinVar Miner

Submissions for variant NM_005654.6(NR2F1):c.404G>A (p.Arg135His)

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
Ambry Genetics RCV004491273 SCV004990790 likely pathogenic Inborn genetic diseases 2023-09-20 criteria provided, single submitter clinical testing The c.404G>A (p.R135H) alteration is located in exon 1 (coding exon 1) of the NR2F1 gene. This alteration results from a G to A substitution at nucleotide position 404, causing the arginine (R) at amino acid position 135 to be replaced by a histidine (H). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Two other alterations at the same codon, c.403C>T (p.R135C) and c.403C>A (p.R135S), have been detected in patients with symptoms consistent with Bosch-Boonstra-Schaaf optic atrophy syndrome. This amino acid position is highly conserved in available vertebrate species. Based on internal structural analysis, R135H is moderately disruptive to the DNA-binding interface of NR2F1, but there are no comparable internally pathogenic variants nearby for comparison (Liu, 2023). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

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.