Submissions for variant NM_138694.4(PKHD1):c.561G>A (p.Trp187Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282947	SCV002571032	likely pathogenic	Autosomal recessive polycystic kidney disease	2022-07-18	criteria provided, single submitter	clinical testing	Variant summary: PKHD1 c.561G>A (p.Trp187X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251132 control chromosomes. To our knowledge, no occurrence of c.561G>A in individuals affected with Polycystic Kidney And Hepatic Disease and no experimental evidence demonstrating its impact on protein function have 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 likely pathogenic.
Invitae	RCV002282947	SCV004317687	pathogenic	Autosomal recessive polycystic kidney disease	2023-08-14	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1704620). This sequence change creates a premature translational stop signal (p.Trp187*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. For these reasons, this variant has been classified as Pathogenic.