ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2725C>T (p.Arg909Ter) (rs727504089)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790818 SCV000228393 pathogenic not provided 2013-12-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000176696 SCV000918010 likely pathogenic Autosomal recessive polycystic kidney disease 2018-10-22 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.2725C>T (p.Arg909X) 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 (e.g. c.3761_3762delinsG (p.Ala1254fsX49), c.5895dupA (p.Leu1966fsX4) and c.9319C>T (p.Arg3107X)). The variant was absent in 276928 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2725C>T 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 RCV000176696 SCV000937061 pathogenic Autosomal recessive polycystic kidney disease 2019-02-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg909*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PKHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 167491). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000176696 SCV001163053 pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing

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