Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002938844 | SCV003271540 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with leucine at codon 1307 of the PKHD1 protein (p.Gln1307Leu). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and leucine. This variant is present in population databases (rs572226863, ExAC 0.009%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 |
RCV003961255 | SCV004779040 | uncertain significance | PKHD1-related disorder | 2024-02-19 | criteria provided, single submitter | clinical testing | The PKHD1 c.3920A>T variant is predicted to result in the amino acid substitution p.Gln1307Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ambry Genetics | RCV004067238 | SCV005006793 | uncertain significance | Inborn genetic diseases | 2023-12-18 | criteria provided, single submitter | clinical testing | The c.3920A>T (p.Q1307L) alteration is located in exon 32 (coding exon 31) of the PKHD1 gene. This alteration results from a A to T substitution at nucleotide position 3920, causing the glutamine (Q) at amino acid position 1307 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |