Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000633428 | SCV000754652 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 375 of the PKHD1 protein (p.Arg375Trp). This variant is present in population databases (rs376040501, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 16133180, 19940839, 27225849; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 528296). 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 expected to disrupt PKHD1 protein function. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000633428 | SCV001163071 | likely pathogenic | Autosomal recessive polycystic kidney disease | criteria provided, single submitter | clinical testing | ||
Revvity Omics, |
RCV001784205 | SCV002024650 | likely pathogenic | Polycystic kidney disease 4 | 2020-05-04 | criteria provided, single submitter | clinical testing | |
3billion | RCV001784205 | SCV002573092 | likely pathogenic | Polycystic kidney disease 4 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.66; 3Cnet: 0.96). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000528296). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 27225849). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
Gene |
RCV000681916 | SCV003915081 | likely pathogenic | not provided | 2023-04-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30586318, 19940839, 31730820, 27225849, 16133180, 33123899) |
Division Of Personalized Genomic Medicine, |
RCV001784205 | SCV004037353 | likely pathogenic | Polycystic kidney disease 4 | 2020-02-24 | criteria provided, single submitter | clinical testing | The c.1123C>T variant is a heterozygous single base pair substitution at nucleotide 1123 in exon 15 of 67 of the PKHD1 gene, resulting in the substitution of a well-conserved, positively charged, Arginine residue at amino acid position 375 to a non-polar Tryptophan residue. The c.1123C>T variant is observed in the Genome Aggregation Database (gnomAD) in heterozygous but not homozygous form indicating it is not a common benign variant in the populations represented in this database. This variant has been observed in trans with a pathogenic variant in individuals with AR Polycystic Kidney Disease (PMID: 16133180, 30595564, 27225849). This variant is classified as likely pathogenic. |
Baylor Genetics | RCV001784205 | SCV004202250 | likely pathogenic | Polycystic kidney disease 4 | 2023-10-10 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000681916 | SCV004226559 | likely pathogenic | not provided | 2022-05-10 | criteria provided, single submitter | clinical testing | PP4, PM2, PM3_strong, PS4_moderate |
Gharavi Laboratory, |
RCV000681916 | SCV000809399 | likely pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research | |
Genomics And Bioinformatics Analysis Resource, |
RCV001784205 | SCV004024147 | likely pathogenic | Polycystic kidney disease 4 | no assertion criteria provided | research |