Submissions for variant NM_206933.4(USH2A):c.2777G>A (p.Arg926His)

gnomAD frequency: 0.00004  dbSNP: rs146916397

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041817	SCV000065513	uncertain significance	not specified	2011-09-17	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Arg926His varia nt in USH2A has not been reported in the literature nor previously identified by our laboratory. Computational analyses (biochemical amino acid properties, homo logy, PolyPhen2, SIFT, AlignGVGD) do not provide strong support for or against p athogenicity. In summary, the clinical significance of this variant cannot be de termined with certainty at this time.
GeneDx	RCV001243252	SCV000523476	uncertain significance	not provided	2024-10-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25078356)
Counsyl	RCV000665768	SCV000789939	uncertain significance	Usher syndrome type 2A; Retinitis pigmentosa 39	2017-02-27	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001074040	SCV001239608	uncertain significance	Retinal dystrophy	2018-11-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001243252	SCV001416398	uncertain significance	not provided	2022-10-13	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 926 of the USH2A protein (p.Arg926His). This variant is present in population databases (rs146916397, gnomAD 0.02%). 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: 48491). 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	RCV003450833	SCV004182400	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003450832	SCV004182401	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV001074040	SCV004708030	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research