ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.14287G>A (p.Gly4763Arg)

dbSNP: rs397517990
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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 (formerly Invitae), Labcorp 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, University Medical Centre Ljubljana 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-Nilou Lab RCV003450788 SCV004183084 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab 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
SingHealth Duke-NUS Institute of Precision Medicine 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, Nagoya University RCV003887895 SCV004707214 uncertain significance Retinal dystrophy 2023-10-01 flagged submission research

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