ClinVar Miner

Submissions for variant NM_001195794.1(CLRN1):c.189C>A (p.Tyr63Ter) (rs111033267)

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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 RCV000844690 SCV000065128 pathogenic Rare genetic deafness 2012-12-24 criteria provided, single submitter clinical testing The Tyr63X variant in CLRN1 has been reported in a homozygous state in three sib lings with Usher syndrome from one family (Adato 2002, Aller 2004). This nonsens e variant leads to a premature termination codon at position 63, which is predic ted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM).
Counsyl RCV000004647 SCV000486175 pathogenic Usher syndrome, type 3A 2016-04-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000004647 SCV000919233 pathogenic Usher syndrome, type 3A 2018-09-07 criteria provided, single submitter clinical testing Variant summary: CLRN1 c.189C>A (p.Tyr63X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.8e-05 in 277198 control chromosomes. c.189C>A has been reported in the literature as a homozygous and compound heterozygous allele in multiple individuals affected with Usher Syndrome Type 3 (Adato_2002; Garcia-Garcia_2012). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000004647 SCV000024821 pathogenic Usher syndrome, type 3A 2004-12-01 no assertion criteria provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505037 SCV000598874 pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research

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