Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000728359 | SCV000855918 | uncertain significance | not provided | 2017-07-20 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002477683 | SCV002788534 | uncertain significance | Polycystic kidney disease 4 | 2022-01-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002533090 | SCV003490174 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2523 of the PKHD1 protein (p.Ile2523Val). This variant is present in population databases (rs146962673, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 593347). 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. 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 | RCV002533091 | SCV003752894 | uncertain significance | Inborn genetic diseases | 2022-12-28 | criteria provided, single submitter | clinical testing | The c.7567A>G (p.I2523V) alteration is located in exon 48 (coding exon 47) of the PKHD1 gene. This alteration results from a A to G substitution at nucleotide position 7567, causing the isoleucine (I) at amino acid position 2523 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |