ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.1055C>T (p.Thr352Ile) (rs780308389)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665487 SCV000789617 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-02-14 criteria provided, single submitter clinical testing
Invitae RCV000804683 SCV000944603 pathogenic not provided 2018-08-20 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.
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 tute.org; 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.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504656 SCV000598763 likely pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research

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