ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.7061G>A (p.Arg2354His)

gnomAD frequency: 0.00007  dbSNP: rs201386640
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cytogenetics and Genomics Laboratory, Medical University of South Carolina RCV000754979 SCV000803389 uncertain significance Leber congenital amaurosis 2018-06-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001246671 SCV001420046 uncertain significance not provided 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2354 of the USH2A protein (p.Arg2354His). This variant is present in population databases (rs201386640, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Usher syndrome (PMID: 17085681). ClinVar contains an entry for this variant (Variation ID: 552369). 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 histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001805789 SCV002050829 uncertain significance not specified 2021-12-08 criteria provided, single submitter clinical testing Variant summary: USH2A c.7061G>A (p.Arg2354His) results in a conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251280 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (6.4e-05 vs 0.011), allowing no conclusion about variant significance. c.7061G>A has been reported in the literature in individuals affected with Usher Syndrome and other conditions with vision and hearing loss (example: Aller_2006, Glen_2019), but these data do not allow any conclusion about variant significance. Co-occurrences with other pathogenic variants have been reported (RPE65 c.1338G>T, p.Arg446Ser), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed this variant since 2014, where all submitters have classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV003451660 SCV004181565 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001835082 SCV004181566 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003451660 SCV004208138 uncertain significance Retinitis pigmentosa 39 2023-11-07 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV001246671 SCV005187238 uncertain significance not provided criteria provided, single submitter not provided
GeneDx RCV001246671 SCV005401152 uncertain significance not provided 2024-05-16 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Identified in a patient with hearing loss, night blindness, and reduced vision who as also heterozygous, phase unknown, for two lpath/path variants in the USH2A gene in published literature (PMID: 17085681); Identified in a patient with Leber congenital amaurosis who is homozygous for a variant in the RPE65 gene and heterozygous for a second variant in the USH2A gene (phase unknown) in published literature (PMID: 30870047); This variant is associated with the following publications: (PMID: 17085681, 30870047)
Counsyl RCV000667613 SCV000792091 uncertain significance Usher syndrome type 2A; Retinitis pigmentosa 39 2017-06-08 no assertion criteria provided clinical testing This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
Natera, Inc. RCV001835082 SCV002090864 uncertain significance Usher syndrome type 2A 2020-01-11 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.