ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.4222C>T (p.Gln1408Ter) (rs746551311)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627213 SCV000748200 pathogenic not provided 2018-10-12 criteria provided, single submitter clinical testing The Q1408X variant has been published previously in association with retinitis pigmentosa (Seyedahmadi et al., 2004; Tajiguli et al., 2016). The variant is not observed in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we consider this variant to be pathogenic.
Counsyl RCV000666545 SCV000790851 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-04-12 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002566 SCV001160539 pathogenic not specified 2019-05-22 criteria provided, single submitter clinical testing The USH2A c.4222C>T; p.Gln1408Ter variant (rs746551311) is reported in the literature in several individuals affected with retinitis pigmentosa or Usher syndrome (Bonnet 2016, Seyedahmadi 2004, Tajiguli 2016). This variant has been observed in affected individuals both in the homozygous state and together with a second pathogenic variant (Bonnet 2016, Tajiguli 2016). This variant is found in the South Asian population with an overall allele frequency of 0.04% (14/30612 alleles) in the Genome Aggregation Database, and it is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 438021). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Bonnet C et al. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients. Eur J Hum Genet. 2016 Dec;24(12):1730-1738. Seyedahmadi BJ et al. Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa. Exp Eye Res. 2004 Aug;79(2):167-73. Tajiguli A et al. Next-generation sequencing-based molecular diagnosis of 12 inherited retinal disease probands of Uyghur ethnicity. Sci Rep. 2016 Feb 9;6:21384.
Invitae RCV000627213 SCV001213763 pathogenic not provided 2020-07-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1408*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs746551311, ExAC 0.05%). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 26856745, 15325563). ClinVar contains an entry for this variant (Variation ID: 438021). 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.
Blueprint Genetics RCV001073573 SCV001239124 pathogenic Retinal dystrophy 2019-06-28 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504899 SCV000598810 pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Natera, Inc. RCV001276258 SCV001462271 pathogenic Usher syndrome, type 2A 2020-09-16 no assertion criteria provided clinical testing

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