Submissions for variant NM_206933.4(USH2A):c.5890C>T (p.Arg1964Cys)

gnomAD frequency: 0.00009  dbSNP: rs148049006

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001248423	SCV001421910	uncertain significance	not provided	2024-09-06	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 1964 of the USH2A protein (p.Arg1964Cys). This variant is present in population databases (rs148049006, gnomAD 0.04%). 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: 972402). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt USH2A protein function with a negative predictive value of 95%. 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.
Dept Of Ophthalmology, Nagoya University	RCV003887973	SCV004707977	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
GeneDx	RCV001248423	SCV005386204	uncertain significance	not provided	2024-02-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20440071)
Laboratory of Prof. Karen Avraham, Tel Aviv University	RCV001835337	SCV005442640	uncertain significance	Usher syndrome type 2A	2024-12-26	criteria provided, single submitter	research	The c.5890C>T:p.(Arg1964Cys) variant is very rare and possibly deleterious. It was detected in an individual with sloping normal-to-severe HL, that carried another USH2A VUS, c.1585A>C:p.(Thr529Pro).
Natera, Inc.	RCV001835337	SCV002091555	uncertain significance	Usher syndrome type 2A	2020-01-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004733215	SCV005367312	uncertain significance	USH2A-related disorder	2024-09-17	no assertion criteria provided	clinical testing	The USH2A c.5890C>T variant is predicted to result in the amino acid substitution p.Arg1964Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.