ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12241C>T (p.Arg4081Trp) (rs144783615)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000217686 SCV000272887 uncertain significance not specified 2016-02-21 criteria provided, single submitter clinical testing The p.Arg4081Trp variant in USH2A has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 28/121364 chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs144783615). Although this variant has been seen in the general popula tion, its frequency is not high enough to rule out a pathogenic role. Computatio nal prediction tools and conservation analysis suggest that this variant may imp act the protein, though this information is not predictive enough to determine p athogenicity. In summary, the clinical significance of the p.Arg4081Trp variant is uncertain.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756891 SCV000884859 uncertain significance not provided 2017-12-29 criteria provided, single submitter clinical testing The USH2A p.Arg4081Trp variant (rs144783615) has not been reported in the medical literature. However, the p.Arg4081Trp is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.14% in the African population (identified in 34 out of 24,020 chromosomes), and it is classified as a variant of uncertain significance in ClinVar (Variant ID: 229617). The arginine at codon 4081 is moderately conserved considering 12 species (Alamut software v2.10.0), and computational analyses predict that this variant does affect the structure/function of the USH2A protein (SIFT: damaging, PolyPhen2: possibly damaging, MutationTaster: disease causing). However, based on the available information, the clinical significance of the p.Arg4081Trp variant cannot be determined with certainty.
Invitae RCV000756891 SCV001197614 likely benign not provided 2020-01-02 criteria provided, single submitter clinical testing

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