Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002583 | SCV001160556 | uncertain significance | Polycystic kidney disease, adult type | 2019-05-03 | criteria provided, single submitter | clinical testing | The PKD1 c.7340C>T; p.Thr2447Met variant (rs760315179) is reported in the literature in an individual affected with autosomal dominant polycystic kidney disease (ADPKD), although this individual also carried several other missense variant which could be causative for disease (Bullich 2018). The p.Thr2447Met variant is found in the general population with an overall allele frequency of 0.01% (26/259570 alleles) in the Genome Aggregation Database. The threonine at codon 2447 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Thr2447Met variant is uncertain at this time. References: Bullich G et al. A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases. Kidney Int. 2018 Aug;94(2):363-371. |
Fulgent Genetics, |
RCV001002583 | SCV002789303 | uncertain significance | Polycystic kidney disease, adult type | 2022-03-24 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003953428 | SCV004780255 | uncertain significance | PKD1-related condition | 2023-11-29 | criteria provided, single submitter | clinical testing | The PKD1 c.7340C>T variant is predicted to result in the amino acid substitution p.Thr2447Met. This variant has been reported in individuals with polycystic kidney disease, but the clinical significance was uncertain (Bullich et al. 2018. PubMed ID: 29801666, Supplementary Table 1; Nielsen et al. 2021. PubMed ID: 33639313, Supplementary Table 2). This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2156548-G-A). Given the relatively high allele frequency in the general population, we suspect that this variant may be benign. At this time, however, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |