Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001962371 | SCV002209024 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 152 of the PKHD1 protein (p.Leu152Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV004042123 | SCV005006797 | uncertain significance | Inborn genetic diseases | 2023-10-05 | criteria provided, single submitter | clinical testing | The c.454C>G (p.L152V) alteration is located in exon 7 (coding exon 6) of the PKHD1 gene. This alteration results from a C to G substitution at nucleotide position 454, causing the leucine (L) at amino acid position 152 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |