ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.5330G>A (p.Arg1777Gln)

gnomAD frequency: 0.00015  dbSNP: rs541275063
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001371075 SCV001567628 uncertain significance not provided 2022-08-04 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 1777 of the USH2A protein (p.Arg1777Gln). This variant is present in population databases (rs541275063, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 33576794). ClinVar contains an entry for this variant (Variation ID: 1061486). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg1777 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21593743, 22135276, 26629787, 26969326). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Genome-Nilou Lab RCV001578959 SCV001806326 uncertain significance Usher syndrome type 2A 2021-07-22 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001578960 SCV001806327 uncertain significance Retinitis pigmentosa 39 2021-07-22 criteria provided, single submitter clinical testing
GeneDx RCV001371075 SCV001825763 uncertain significance not provided 2021-12-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33576794)
Natera, Inc. RCV001578959 SCV002091569 uncertain significance Usher syndrome type 2A 2020-03-20 no assertion criteria provided clinical testing

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.