Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001386689 | SCV001587026 | pathogenic | Autosomal recessive polycystic kidney disease | 2020-03-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala3804Glyfs*9) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant has been observed in individual(s) with polycystic kidney disease (PMID: 16133180). This variant is not present in population databases (ExAC no frequency). |
| Breakthrough Genomics, |
RCV004596452 | SCV005088860 | pathogenic | Polycystic kidney disease 4 | 2020-11-17 | criteria provided, single submitter | clinical testing | This variant is predicted to cause a frameshift and consequent premature termination of the protein and the resultant protein will likely to lack the transmembrane and c-terminal cytoplasmic domains of the protein [UniProt]; this will likely result in loss-of-function. Due to the introduction of a premature stop codon, this aberrant transcript will likely be targeted by the nonsense-mediated mRNA decay (NMD) mechanism [PMID: 15040442]. The variant seems to be a novel variant, as it has not been previously reported in population databases or in the literature. However, several other truncating variants lying downstream of the variant, have been previously reported as ‘pathogenic/likely pathogenic’ in the ClinVar database context of autosomal recessive polycystic kidney disease. |