ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.1927C>T (p.Arg643Ter) (rs727504301)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824734 SCV000203994 pathogenic Rare genetic deafness 2014-02-10 criteria provided, single submitter clinical testing The Arg643X variant in PCDH15 has been reported in two individuals with Usher sy ndrome (Ahmed 2003, Roux 2006), and was not identified in large population studi es. Both of these individuals were homozygous or compound heterozygous with a se cond pathogenic variant and this variant segregated in two affected siblings. Th is nonsense variant leads to a premature termination codon at position 643, whic h is predicted to lead to a truncated or absent protein. In summary, this varian t meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/L MM).
Integrated Genetics/Laboratory Corporation of America RCV000154331 SCV000917971 pathogenic Usher syndrome, type 1F 2018-09-07 criteria provided, single submitter clinical testing Variant summary: PCDH15 c.1927C>T (p.Arg643X) 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. A truncation downstream of this position have been classified as pathogenic by our laboratory (c.2971C>T (p.Arg991X)). The variant was absent in 246434 control chromosomes (gnomAD and publication data). c.1927C>T has been reported in the literature as a homozygous and compound heterozygous allele in multiple individuals affected with Usher Syndrome Type 1F (Ahmed 2003, Roux 2006). 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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