Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041756 | SCV000065452 | likely pathogenic | Rare genetic deafness | 2010-09-27 | criteria provided, single submitter | clinical testing | The Gly4763Arg variant in USH2A has been reported in an individual with Usher sy ndrome and in an individual with nonsyndromic retinitis pigmentosa (McGee 2010). In addition, this residue is conserved in mammals. Furthermore, we have identif ied the Gly4763Arg variant in combination with a pathogenic USH2A variant in two siblings with Usher syndrome. In summary, this variant is likely to be pathogen ic. |
Counsyl | RCV000665736 | SCV000789903 | likely pathogenic | Usher syndrome type 2A; Retinitis pigmentosa 39 | 2017-10-09 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001057445 | SCV001221940 | pathogenic | not provided | 2024-02-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 4763 of the USH2A protein (p.Gly4763Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Usher syndrome (PMID: 25649381, 27460420). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 48433). 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. |
Centre for Mendelian Genomics, |
RCV001198544 | SCV001369522 | likely pathogenic | Usher syndrome type 2A | 2019-10-28 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3. |
Genome- |
RCV003450788 | SCV004183084 | likely pathogenic | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001198544 | SCV004183085 | likely pathogenic | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003450788 | SCV004208299 | pathogenic | Retinitis pigmentosa 39 | 2024-03-22 | criteria provided, single submitter | clinical testing | |
Sing |
RCV003450788 | SCV005881591 | likely pathogenic | Retinitis pigmentosa 39 | 2025-02-05 | criteria provided, single submitter | clinical testing | Another variant with the same amino acid change has been classified as pathogenic/likely pathogenic (PS1, p.Gly4763Arg). Variant is located in a mutational hotspot where >50% of variants are pathogenic (PM1). Variant is not found in gnomAD genomes and homozygous allele count in gnomAD exomes is less than 0 (PM2). Other variants at this amino acid residue have been classified as pathogenic/likely pathogenic (PM5, p.Gly4763Glu; p.Gly4763Val) |
Dept Of Ophthalmology, |
RCV003887895 | SCV004707214 | uncertain significance | Retinal dystrophy | 2023-10-01 | flagged submission | research |