Submissions for variant NM_206933.4(USH2A):c.9356G>A (p.Arg3119His)

gnomAD frequency: 0.00006  dbSNP: rs199885325

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000761698	SCV000891879	uncertain significance	not provided	2018-04-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000761698	SCV001419123	uncertain significance	not provided	2022-03-23	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 3119 of the USH2A protein (p.Arg3119His). This variant is present in population databases (rs199885325, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Usher syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 623717). 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. This variant disrupts the p.Arg3119 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 27460420), which suggests that this may be a clinically significant amino acid residue. 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.
GeneDx	RCV000761698	SCV002000643	uncertain significance	not provided	2024-07-03	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab	RCV003453580	SCV004182704	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001835953	SCV004182705	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001835953	SCV002088405	uncertain significance	Usher syndrome type 2A	2020-02-15	no assertion criteria provided	clinical testing