Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000598361 | SCV000707407 | uncertain significance | not provided | 2018-06-05 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000665545 | SCV000789687 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-02-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000598361 | SCV001985429 | uncertain significance | not provided | 2021-04-05 | criteria provided, single submitter | clinical testing | Identified in a patient with ARPKD with a second variant in an unknown phase in published literature (Sharp et al., 2005); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15805161) |
Invitae | RCV000665545 | SCV003250282 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1804 of the PKHD1 protein (p.Arg1804Cys). This variant is present in population databases (rs201906247, gnomAD 0.08%). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15805161). ClinVar contains an entry for this variant (Variation ID: 501154). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PKHD1 protein function. 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 |
RCV003420040 | SCV004115791 | uncertain significance | PKHD1-related condition | 2022-12-24 | criteria provided, single submitter | clinical testing | The PKHD1 c.5410C>T variant is predicted to result in the amino acid substitution p.Arg1804Cys. This variant has been reported with a canonical splice variant (c.5381-2A>C) in a fetal specimen due to suspected autosomal recessive polycystic kidney disease (ARPKD) (Sharp et al. 2005. PubMed ID: 15805161). This variant was also described in a large cohort of individuals with suspected early-onset chronic kidney disease (Domingo-Gallego et al. 2022. PubMed ID: 33532864, supplementary data). This variant is reported in 0.078% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51882398-G-A). This variant could be pathogenic. At this time, however, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |