ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12361C>T (p.Arg4121Cys)

gnomAD frequency: 0.00002  dbSNP: rs772357461
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 RCV001312540 SCV001502998 uncertain significance not provided 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 4121 of the USH2A protein (p.Arg4121Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs772357461, ExAC 0.002%). This missense change has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 31054281). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
GeneDx RCV001312540 SCV004168525 uncertain significance not provided 2023-04-28 criteria provided, single submitter clinical testing Identified in a patient with an inherited retinal disease who also harbored p.(R4121C) and p.(R1946*) phase unknown in published literature (Zhu et al., 2020); Identified in a patient with an inherited retinal disease who also harbored p.(V4374E) phase unknown in published literature (Gao et al., 2020); Identified in a cohort of patients with suspected inherited retinal disease in published literature (Gao et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32675063, 32188678, 31054281)
Genome-Nilou Lab RCV003449892 SCV004182008 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001835527 SCV004182009 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001835527 SCV002088308 uncertain significance Usher syndrome type 2A 2020-04-22 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.