ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.653T>A (p.Val218Glu) (rs397518026)

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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 RCV000041890 SCV000065586 pathogenic Rare genetic deafness 2016-08-09 criteria provided, single submitter clinical testing The p.Val218Glu variant in USH2A has been reported in at least 8 individuals wit h Usher syndrome, all of whom carried a second, pathogenic USH2A variant on the other allele (Leroy 2001, Cremers 2007, Baux 2007, Herrera 2008, Bonnet 2011, Gl ockle 2013, Besnard 2014). This variant has also been identified in 5/66590 Euro pean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs397518026). Although it has been seen in the general populat ion, its frequency is low enough to be consistent with a recessive carrier frequ ency. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner based upon its occurrence in tr ans with known pathogenic USH2A variants in multiple affected individuals.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000408647 SCV000484497 uncertain significance not provided 2015-09-24 criteria provided, single submitter clinical testing
Invitae RCV000408647 SCV000963510 likely pathogenic not provided 2018-07-30 criteria provided, single submitter clinical testing This sequence change replaces valine with glutamic acid at codon 218 of the USH2A protein (p.Val218Glu). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glutamic acid. This variant is present in population databases (rs397518026, ExAC 0.008%). This variant has been observed in several individuals affected with Usher syndrome (PMID: 11311042, 16963483, 17405132, 18281613, 21569298, 24498627, 28944237). ClinVar contains an entry for this variant (Variation ID: 48564). 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"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504825 SCV000598821 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Counsyl RCV000675152 SCV000800758 pathogenic Retinitis pigmentosa 39 2017-04-20 no assertion criteria provided clinical testing

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