Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169490 | SCV000220944 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2014-12-10 | criteria provided, single submitter | literature only | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169490 | SCV000918006 | pathogenic | Autosomal recessive polycystic kidney disease | 2018-02-02 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.10452dupT (p.Leu3485SerfsX18) 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 (eg. c.10637delT/p.Val3546fsX22, c.11314C>T/p.Arg3772X). The variant allele was found at a frequency of 4.1e-06 in 245374 control chromosomes. c.10452dupT has been reported in the literature in individuals affected with Polycystic Kidney and Hepatic Disease. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory classified this variant as likely pathogenic. Many truncation variants downstream have been reported in affected individuals, such as c.10639dupC, c.11339dupC, c.11408dupA, and c.11538dupT, suggesting the functional importance of the C-terminal region of this protein. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000169490 | SCV000946312 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-09-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189084). This premature translational stop signal has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15108281, 19914852). This variant is present in population databases (rs771623148, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Leu3485Serfs*18) 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). |
Department of Molecular and Human Genetics, |
RCV000169490 | SCV001334117 | pathogenic | Autosomal recessive polycystic kidney disease | 2020-04-16 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002492694 | SCV002788218 | pathogenic | Polycystic kidney disease 4 | 2021-11-16 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV002492694 | SCV004204539 | pathogenic | Polycystic kidney disease 4 | 2023-09-16 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000169490 | SCV002075513 | pathogenic | Autosomal recessive polycystic kidney disease | 2017-07-28 | no assertion criteria provided | clinical testing | |
Yale Center for Mendelian Genomics, |
RCV000169490 | SCV002106573 | pathogenic | Autosomal recessive polycystic kidney disease | 2019-01-17 | no assertion criteria provided | literature only |