ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2971C>T (p.Arg991Ter) (rs754391973)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781698 SCV000919961 pathogenic Usher syndrome type 1F 2018-03-02 criteria provided, single submitter clinical testing Variant summary: PCDH15 c.2971C>T (p.Arg991X) 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 2e-05 in 246060 control chromosomes. This frequency is not higher than expected for a pathogenic variant in PCDH15 causing Usher Syndrome Type 1F (2e-05 vs 0.0032), allowing no conclusion about variant significance. The c.2971C>T variant has been reported in the literature in multiple homozygous individuals affected with Usher Syndrome Type 1F. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001386497 SCV001586741 pathogenic not provided 2020-08-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg991*) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs754391973, ExAC 0.005%). This variant has been observed in individual(s) with clinical features of Usher syndrome (PMID: 16679490, 24618850, 29568747). It has also been observed to segregate with disease in related individuals. This variant is also known as c.2758C>T (p.R920*) in the literature. ClinVar contains an entry for this variant (Variation ID: 224747). Loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705). For these reasons, this variant has been classified as Pathogenic.
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000210315 SCV000259086 pathogenic Usher syndrome type 1D 2015-08-28 no assertion criteria provided clinical testing

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