ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.2653C>T (p.His885Tyr) (rs746071929)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665157 SCV000789226 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-01-24 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778220 SCV000914386 uncertain significance Retinitis pigmentosa 2019-01-10 criteria provided, single submitter clinical testing The USH2A c.2653C>T (p.His885Tyr) missense variant has been reported in two studies in which it is found in a total of three individuals with retinitis pigmentosa. The variant was identified in two of these individuals in a compound heterozygous state with a second splice site variant (Xu et al. 2014). The third individual carried two previously reported missense variants in addition to the p.His885Tyr variant, the phase of which were not given (Oishi et al. 2014). The p.His885Tyr variant was absent from 96 controls but is reported at a frequency of 0.00081 in the East Asian population of the Exome Aggregation Consortium. Based on the evidence, the USH2 p.His885Tyr variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Blueprint Genetics RCV001075434 SCV001241057 uncertain significance Retinal dystrophy 2018-08-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001098933 SCV001255334 uncertain significance Usher syndrome, type 2A 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001244238 SCV001417444 uncertain significance not provided 2019-10-05 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 885 of the USH2A protein (p.His885Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs746071929, ExAC 0.08%). This variant has been observed in several individuals affected with retinitis pigmentosa (PMID: 24938718). ClinVar contains an entry for this variant (Variation ID: 550419). 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.

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