Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756504 | SCV000884335 | uncertain significance | Polycystic kidney disease, adult type | 2020-02-03 | criteria provided, single submitter | clinical testing | The PKD1 c.9377C>T; p.Thr3126Ile variant is reported in the literature in multiple individuals affected with autosomal dominant polycystic kidney disease, and segregates with the disorder in at least one family (Audrezet 2011, Liu 2015). This variant is reported in ClinVar (Variation ID: 618295), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The threonine at codon 3126 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of functional data and limited clinical data, the significance of the p.Thr3126Ile variant is uncertain at this time. References: Audrezet M et al. Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum Mutat. 2012; 33(8):1239-50. Liu Y et al. Targeted Next-Generation Sequencing for Clinical Diagnosis of 561 Mendelian Diseases. PLoS One. 2015 Aug 14;10(8):e0133636. |
| Ambry Genetics | RCV002533791 | SCV003582102 | likely pathogenic | Inborn genetic diseases | 2024-07-10 | criteria provided, single submitter | clinical testing | The c.9377C>T (p.T3126I) alteration is located in exon 26 (coding exon 26) of the PKD1 gene. This alteration results from a C to T substitution at nucleotide position 9377, causing the threonine (T) at amino acid position 3126 to be replaced by an isoleucine (I). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was identified in several individuals with autosomal dominant polycystic kidney disease and was reported to segregate with disease in one family (Audrézet, 2012; Liu, 2015, Mochizuki, 2019). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
| Genomic Medicine Center of Excellence, |
RCV000756504 | SCV005374511 | likely pathogenic | Polycystic kidney disease, adult type | 2024-09-22 | criteria provided, single submitter | clinical testing |