Submissions for variant NM_206933.4(USH2A):c.9355C>T (p.Arg3119Cys)

gnomAD frequency: 0.00003  dbSNP: rs576236830

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674954	SCV000800370	uncertain significance	Usher syndrome type 2A; Retinitis pigmentosa 39	2018-06-01	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376260	SCV001573339	uncertain significance	Retinitis pigmentosa 39	2021-04-08	criteria provided, single submitter	research	The USH2A c.9355C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000674954	SCV002791726	uncertain significance	Usher syndrome type 2A; Retinitis pigmentosa 39	2022-05-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001725194	SCV003296571	uncertain significance	not provided	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3119 of the USH2A protein (p.Arg3119Cys). This variant is present in population databases (rs576236830, gnomAD 0.03%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 27460420). ClinVar contains an entry for this variant (Variation ID: 558652). 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 not expected to disrupt USH2A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV001376260	SCV004182706	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453392	SCV004182707	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001725194	SCV001960081	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001725194	SCV001972889	uncertain significance	not provided		no assertion criteria provided	clinical testing