ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.6937G>T (p.Gly2313Cys)

gnomAD frequency: 0.00014  dbSNP: rs199840367
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000432643 SCV000525066 likely pathogenic not provided 2023-04-18 criteria provided, single submitter clinical testing 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: 34758253, 27032803, 26261414, 26306921, 34426522, 31589614, 31456290, 34335733, 28981474)
CeGaT Center for Human Genetics Tuebingen RCV000432643 SCV000891881 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing
Invitae RCV000432643 SCV001202175 pathogenic not provided 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2313 of the USH2A protein (p.Gly2313Cys). This variant is present in population databases (rs199840367, gnomAD 0.02%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 26261414, 26306921, 27032803, 28981474; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 384319). 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 USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074794 SCV001240391 pathogenic Retinal dystrophy 2019-07-03 criteria provided, single submitter clinical testing
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill RCV001095706 SCV001251524 likely pathogenic Retinitis pigmentosa 39 criteria provided, single submitter research The USH2A c.6937G>T (p.G2313C) variant has been reported in the compound heterozygous state in individuals with isolated RP (PMID: 26261414; 26306921; 27032803; 28981474).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271497 SCV002555737 pathogenic Usher syndrome 2023-12-14 criteria provided, single submitter clinical testing Variant summary: USH2A c.6937G>T (p.Gly2313Cys) results in a non-conservative amino acid change located in the Fibronectin type III repeat domain (IPR003961) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 250934 control chromosomes (gnomAD). This frequency is not higher than the estimated maximum expected for a pathogenic variant in USH2A causing Usher Syndrome (0.011), allowing no conclusion about variant significance. c.6937G>T has been reported in the literature in multiple individuals affected with retinitis pigmentosa (e.g. Sharon_2015, Bravo-Gil_2016, Comander_2017, Koyanagi_2019, Jauregui_2020, Karali_2022, Ganapathi_2022, Sen_2023). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine other submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Genetics and Molecular Pathology, SA Pathology RCV002272234 SCV002556442 uncertain significance Cone-rod dystrophy 3 2021-04-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004533027 SCV004113879 pathogenic USH2A-related disorder 2022-11-10 criteria provided, single submitter clinical testing The USH2A c.6937G>T variant is predicted to result in the amino acid substitution p.Gly2313Cys. This variant has been reported in the compound heterozygous state in two siblings with autosomal recessive retinitis pigmentosa (arRP) (Bravo-Gil et al. 2016. PubMed ID: 27032803). It was also identified in the compound heterozygous state in another patient with arRP (Beryozkin et al. 2015. PubMed ID: 26306921, Table 1, MOL1234). Also, this variant was reported in another patient with non-syndromic retinitis pigmentosa. No other information was provided in this study (Sharon and Banin. 2015. PubMed ID: 26261414, Table 2). It was recently reported in the heterozygous state in a patient with pericentral RP. This patient was also heterozygous in USH2A for a known pathogenic nonsense variant and a second rare missense variant (Comander et al. 2017. PubMed ID: 28981474, Family #26 in Table 2). We have also observed the c.6937G>T variant along with a second pathogenic variant in two patients at PreventionGenetics. Taken together, we interpret this variant as pathogenic.
Baylor Genetics RCV001095706 SCV004207723 likely pathogenic Retinitis pigmentosa 39 2023-10-26 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000432643 SCV004238796 likely pathogenic not provided 2023-05-26 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001074794 SCV004707956 uncertain significance Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003992295 SCV004810330 likely pathogenic Usher syndrome type 2A 2024-04-04 criteria provided, single submitter clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center RCV001003268 SCV001161351 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research
Genomics England Pilot Project, Genomics England RCV001095706 SCV001760015 pathogenic Retinitis pigmentosa 39 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.