ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.1111_1112del (p.Ile371fs) (rs1366496013)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Institute Rare Disease Group, Broad Institute RCV000588348 SCV000693911 pathogenic Usher syndrome, type 2A 2017-06-25 criteria provided, single submitter research Reportedly 1 case with this variant in the supplement but that is not available at the time of review (broken link). In trans to a known pathogenic variant. In gnomAD, not found in exomes, once in genomes (1/30960 chromosomes). (PM2, PM3, PVS1).
Counsyl RCV000668783 SCV000793437 likely pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-08-16 criteria provided, single submitter clinical testing
Invitae RCV000804948 SCV000944888 pathogenic not provided 2018-11-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile371Phefs*3) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with retinitis pigmentosa (PMID: 18641288). ClinVar contains an entry for this variant (Variation ID: 495336). 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.
GeneDx RCV000804948 SCV001167832 pathogenic not provided 2018-06-04 criteria provided, single submitter clinical testing The c.1111_1112delAT variant in the USH2A gene has been reported previously in association with Usher syndrome (Sandberg et al., 2008). The c.1111_1112delAT variant causes a frameshift starting with codon Isoleucine 371, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Ile371PhefsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1111_1112delAT variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1111_1112delAT as a pathogenic variant.
Blueprint Genetics RCV001073236 SCV001238772 likely pathogenic Retinal dystrophy 2018-08-09 criteria provided, single submitter clinical testing

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