ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.1000C>T (p.Arg334Trp) (rs397517963)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000213203 SCV000271469 pathogenic Rare genetic deafness 2015-04-27 criteria provided, single submitter clinical testing The p.Arg334Trp variant in USH2A has been reported in 9 probands with Usher synd rome who were either compound heterozygous or homozygous, and segregated in 9 fa mily members (Adato 2000, Auslender 2008, Baux 2014, Baux 2007, Dreyer 2000, Jai jo 2009, Krawitz 2014, Ouyang 2004). This variant has been identified in 4/11496 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs397517963), however this frequency is low enough to be co nsistent with a recessive carrier frequency. In summary, this variant meets our criteria to be classified as pathogenic for autosomal recessive Usher syndrome b ased on multiple reports with pathogenic USH2A variants in individuals with Ushe r syndrome (http://personalizedmedicine.partners.org/).
Counsyl RCV000668930 SCV000793608 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-08-30 criteria provided, single submitter clinical testing
Invitae RCV000822071 SCV000962856 pathogenic not provided 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 334 of the USH2A protein (p.Arg334Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs397517963, ExAC 0.03%). This variant has been observed to segregate with Usher syndrome in a family (PMID: 18452394) and in combination with another USH2A variant in several individuals affected with the same condition (PMID: 18452394, 10909849, 28894305, 19683999, 17405132, 15025721, 27032803, 29142287, 28944237, 25333064, 26338283, 20513143). ClinVar contains an entry for this variant (Variation ID: 228411). 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"). This variant disrupts the p.Arg334 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 17405132), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074876 SCV001240480 pathogenic Retinal dystrophy 2019-08-08 criteria provided, single submitter clinical testing
Sharon lab,Hadassah-Hebrew University Medical Center RCV001003287 SCV001161370 pathogenic Usher syndrome type 2 2019-06-23 no assertion criteria provided research

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