Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000538644 | SCV000629933 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 49 of the PKHD1 gene. It does not directly change the encoded amino acid sequence of the PKHD1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs199953233, ExAC 0.05%). This variant has not been reported in the literature in individuals with PKHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 458606). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Prevention |
RCV003962476 | SCV004778363 | likely benign | PKHD1-related disorder | 2022-11-09 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Natera, |
RCV000538644 | SCV001459183 | uncertain significance | Autosomal recessive polycystic kidney disease | 2020-09-16 | no assertion criteria provided | clinical testing |