Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000412022 | SCV000486701 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2016-07-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000412022 | SCV002231231 | pathogenic | Autosomal recessive polycystic kidney disease | 2021-04-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371184). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe3371Ilefs*3) 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). |
Victorian Clinical Genetics Services, |
RCV002470850 | SCV002769165 | pathogenic | Polycystic kidney disease 4 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous duplication variant, NM_138694.3(PKHD1):c.10109dup, has been identified in exon 60 of 67 of the PKHD1 gene. This duplication is predicted to create a frameshift starting at amino acid position 3371, introducing a stop codon 3 residues downstream (NP_619639.3 (PKHD1):p.(Phe3371Ilefs*3)), resulting in loss of normal protein function through nonsense-mediated decay (NMD). This variant is predicted to result in loss of protein function through nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G). The variant has been previously described as likely pathogenic (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC. |
Prevention |
RCV003401390 | SCV004111420 | pathogenic | PKHD1-related disorder | 2023-05-04 | criteria provided, single submitter | clinical testing | The PKHD1 c.10109dupT variant is predicted to result in a frameshift and premature protein termination (p.Phe3371Ilefs*3). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been interpreted as pathogenic/likely pathogenic in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/371184/). Frameshift variants in PKHD1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Baylor Genetics | RCV002470850 | SCV004204673 | likely pathogenic | Polycystic kidney disease 4 | 2023-04-26 | criteria provided, single submitter | clinical testing |