ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1606T>C (p.Cys536Arg) (rs111033273)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413438 SCV000490868 pathogenic not provided 2016-02-22 criteria provided, single submitter clinical testing The C536R variant has been reported many times in association with Usher syndrome (Dreyer et al., 2000; Pennings et al., 2004; Pennings et al., 2004; Bonnet et al., 2011; Le Quesne et al., 2012). The C536R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C536R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret this variant to be pathogenic.
Invitae RCV000413438 SCV001208805 pathogenic not provided 2019-09-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 536 of the USH2A protein (p.Cys536Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs111033273, ExAC 0.001%). This variant has been observed in individuals and families affected with Usher syndrome (PMID: 10909849, 28559085). ClinVar contains an entry for this variant (Variation ID: 48471). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074602 SCV001240193 pathogenic Retinal dystrophy 2019-01-16 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041794 SCV000065490 pathogenic Rare genetic deafness 2007-04-18 no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000678646 SCV000804736 pathogenic Retinitis pigmentosa 39 2016-09-01 no assertion criteria provided clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787727 SCV000926727 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Counsyl RCV000984314 SCV001132497 pathogenic Usher syndrome, type 2A 2016-11-18 no assertion criteria provided clinical testing
Counsyl RCV000678646 SCV001132498 pathogenic Retinitis pigmentosa 39 2016-11-18 no assertion criteria provided clinical testing

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