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

gnomAD frequency: 0.00003  dbSNP: rs111033273

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413438	SCV000490868	pathogenic	not provided	2019-07-18	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 27957503, 10909849, 15043528, 16963483, 14676276, 27068579, 18273898, 31047448, 28944237, 28574513, 27318125, 26927203, 28559085, 22135276, 21738395, 21569298, 21151602, 15241801, 33576794)
Invitae	RCV000413438	SCV001208805	pathogenic	not provided	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 536 of the USH2A protein (p.Cys536Arg). This variant is present in population databases (rs111033273, gnomAD 0.004%). This missense change has been observed in individuals with Usher syndrome (PMID: 10909849, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 48471). 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	RCV001074602	SCV001240193	pathogenic	Retinal dystrophy	2019-01-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000413438	SCV001500879	pathogenic	not provided	2020-10-01	criteria provided, single submitter	clinical testing
The Shared Resource Centre "Genome", Research Centre for Medical Genetics	RCV000984314	SCV002756441	pathogenic	Usher syndrome type 2A	2022-11-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483034	SCV002788576	pathogenic	Usher syndrome type 2A; Retinitis pigmentosa 39	2022-05-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000678646	SCV004182516	pathogenic	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000984314	SCV004182518	pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000678646	SCV004208225	pathogenic	Retinitis pigmentosa 39	2023-10-02	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041794	SCV000065490	pathogenic	Rare genetic deafness	2007-04-18	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000678646	SCV000804736	pathogenic	Retinitis pigmentosa 39	2016-09-01	no assertion criteria provided	clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, 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
Natera, Inc.	RCV000984314	SCV001452257	pathogenic	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000413438	SCV001917856	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000413438	SCV001955038	pathogenic	not provided		no assertion criteria provided	clinical testing