ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.8740C>T (p.Arg2914Ter) (rs766590491)

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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 RCV000213731 SCV000271475 pathogenic Rare genetic deafness 2015-04-24 criteria provided, single submitter clinical testing The p.Arg2914X variant in USH2A has been previously reported in 4 individuals wi th Usher syndrome (Baux 2014, McGee 2010) and 1 individual with retinitis pigmen tosa (RP) (Zhao 2015), however hearing loss was not evaluated in the latter. At least 4 of these individuals were compound heterozygous for a second pathogenic variant in USH2A. This variant has been identified in 1/66678 European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org), though this frequency is low enough to be consistent with a recessive carrier fr equency. This nonsense variant leads to a premature termination codon at positio n 2914, which is predicted to lead to a truncated or absent protein. Loss of fun ction of the USH2A gene is an established disease mechanism in Usher syndrome. I n summary, the p.Arg2914X variant in USH2A meets our criteria to be classified a s pathogenic for autosomal recessive Usher syndrome based upon the predicted imp act to the protein and the previously reported individuals with Usher syndrome ( www.partners.org/personalizedmedicine/lmm).
Blueprint Genetics RCV001075409 SCV001241031 pathogenic Retinal dystrophy 2018-07-21 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091129 SCV001246994 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Invitae RCV001091129 SCV001399316 pathogenic not provided 2019-10-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2914*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs766590491, ExAC 0.001%). This variant has been observed in several individuals with USH2A-related conditions (PMID: 24944099, 25472526). ClinVar contains an entry for this variant (Variation ID: 228417). Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000666615 SCV000790935 pathogenic Retinitis pigmentosa 39 2017-04-14 no assertion criteria provided clinical testing

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