Submissions for variant NM_206933.3(USH2A):c.6670G>T (p.Gly2224Cys) (rs149553844)

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Total submissions: 7

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000191140	SCV000245549	uncertain significance	Retinitis pigmentosa 39	2013-04-10	criteria provided, single submitter	clinical testing	This variant was found once in our laboratory with a pathogenic variant [E767fs] and another missense variant [E3448K; phase undetermined] in a 32-year-old female with retinitis pigmentosa. Variant possibly pathogenic in recessive state; heterozygotes would be carriers.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000359124	SCV000339980	uncertain significance	not provided	2016-04-04	criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000765068	SCV000896268	uncertain significance	Usher syndrome, type 2A; Retinitis pigmentosa 39	2018-10-31	criteria provided, single submitter	clinical testing
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals	RCV001002722	SCV001156415	pathogenic	Usher syndrome, type 2A	2019-02-01	criteria provided, single submitter	clinical testing
Invitae	RCV000359124	SCV001217863	uncertain significance	not provided	2020-01-03	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with cysteine at codon 2224 of the USH2A protein (p.Gly2224Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs149553844, ExAC 0.08%). This variant has been observed in individuals affected with USH2A-related retinopathy (PMID: 25412400, 27160483). In more than one individual, this variant occurred with two additional USH2A variants, making the contribution of p.Gly2224Cys unclear (PMID: 27160483, PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 209202). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Blueprint Genetics	RCV001073314	SCV001238852	uncertain significance	Retinal dystrophy	2018-11-09	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504652	SCV000598823	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research

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