Submissions for variant NM_206933.4(USH2A):c.10373C>T (p.Thr3458Met)

gnomAD frequency: 0.00001  dbSNP: rs149485593

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001073726	SCV001239285	uncertain significance	Retinal dystrophy	2017-09-01	criteria provided, single submitter	clinical testing
Invitae	RCV001239539	SCV001412418	uncertain significance	not provided	2022-07-12	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 3458 of the USH2A protein (p.Thr3458Met). This variant is present in population databases (rs149485593, gnomAD 0.004%). 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: 866029). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The methionine 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	RCV003455331	SCV004182573	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001828534	SCV004182574	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001828534	SCV002088363	uncertain significance	Usher syndrome type 2A	2020-09-22	no assertion criteria provided	clinical testing