ClinVar Miner

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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