Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002886523 | SCV003253361 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with valine at codon 3963 of the PKHD1 protein (p.Glu3963Val). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and valine. 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 conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, 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. |
| Ambry Genetics | RCV003348930 | SCV004061456 | uncertain significance | Inborn genetic diseases | 2023-08-21 | criteria provided, single submitter | clinical testing | The c.11888A>T (p.E3963V) alteration is located in exon 67 (coding exon 66) of the PKHD1 gene. This alteration results from a A to T substitution at nucleotide position 11888, causing the glutamic acid (E) at amino acid position 3963 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |