ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1055C>T (p.Thr352Ile) (rs780308389)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824796 SCV000709742 pathogenic Rare genetic deafness 2017-04-11 criteria provided, single submitter clinical testing The p.Thr352Ile variant in USH2A has been reported in at least 7 individuals wit h Usher syndrome, 5 of whom carried a second pathogenic variant on the other all ele (Baux 2007, Cremers 2007, Dreyer 2008, Bonnet 2011, Besnard 2013, Lenarduzzi 2015, Bonnet 2016). This variant has also been identified in 2/111896 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinsti; dbSNP rs780308389). This frequency in the general population is low en ough to be consistent with a recessive carrier frequency for Usher syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosoma l recessive Usher syndrome based on multiple occurrences with a second pathogeni c variant in affected individuals.
Invitae RCV000804683 SCV000944603 pathogenic not provided 2020-05-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 352 of the USH2A protein (p.Thr352Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs780308389, ExAC 0.003%). This variant has been observed in several individuals and families with USH2A-related conditions (PMID: 28653555, 29142287, 17405132, 25575603, 24498627). ClinVar contains an entry for this variant (Variation ID: 438002). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075415 SCV001241038 pathogenic Retinal dystrophy 2018-08-06 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000665487 SCV001573413 likely pathogenic Retinitis pigmentosa 39 2021-04-08 criteria provided, single submitter research The USH2A c.1055C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM1-S. Based on this evidence we have classified this variant as Likely Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504656 SCV000598763 likely pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research
Counsyl RCV000665487 SCV000789617 likely pathogenic Retinitis pigmentosa 39 2017-02-14 no assertion criteria provided clinical testing

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