Submissions for variant NM_206933.4(USH2A):c.13484G>A (p.Arg4495His)

gnomAD frequency: 0.00004  dbSNP: rs550096037

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000994244	SCV001147662	uncertain significance	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001074070	SCV001239639	uncertain significance	Retinal dystrophy	2018-12-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000994244	SCV001414861	uncertain significance	not provided	2022-07-18	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4495 of the USH2A protein (p.Arg4495His). This variant is present in population databases (rs550096037, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 806349). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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	RCV003455025	SCV004183161	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001827144	SCV004183162	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001827144	SCV002088257	uncertain significance	Usher syndrome type 2A	2020-01-27	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544995	SCV004791423	likely benign	USH2A-related disorder	2019-02-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).