Submissions for variant NM_138694.4(PKHD1):c.5485C>T (p.Gln1829Ter)

gnomAD frequency: 0.00001  dbSNP: rs774759689

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000410933	SCV000486497	likely pathogenic	Autosomal recessive polycystic kidney disease	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000410933	SCV001390386	pathogenic	Autosomal recessive polycystic kidney disease	2023-09-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 371036). This premature translational stop signal has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 19940839, 24162162). This variant is present in population databases (rs774759689, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln1829*) 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000410933	SCV001774749	pathogenic	Autosomal recessive polycystic kidney disease	2021-07-27	criteria provided, single submitter	clinical testing	Variant summary: PKHD1 c.5485C>T (p.Gln1829X) 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 allele was found at a frequency of 4e-06 in 251064 control chromosomes. c.5485C>T has been reported in the literature in multiple individuals affected with Polycystic Kidney And Hepatic Disease (e.g. Krall_2014, Bullich_2018). These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV003463799	SCV004204654	pathogenic	Polycystic kidney disease 4	2023-05-25	criteria provided, single submitter	clinical testing
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center	RCV001844829	SCV001876983	pathogenic	Autosomal dominant polycystic liver disease	2021-09-01	no assertion criteria provided	research
Natera, Inc.	RCV000410933	SCV002078081	pathogenic	Autosomal recessive polycystic kidney disease	2017-08-31	no assertion criteria provided	clinical testing