Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756525 | SCV000884360 | likely pathogenic | not provided | 2018-02-02 | criteria provided, single submitter | clinical testing | The PKD1 c.7109G>C; p.Cys2370Ser variant is not reported in the medical literature, but other nucleotide changes (c.7108T>A, c.7110T>A) causing the same amino acid alteration are reported in the literature in individuals affected with autosomal dominant polycystic kidney disease (ADPKD) (see Mayo ADPKD link, Audrezet 2016, Bataille 2011, Rossetti 2007). Additionally, another variant at this codon (c.7108T>C, p.Cys2370Arg) has also been identified in individuals with ADPKD (see Mayo ADPKD link, Rossetti 2003).The c.7109G>C variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The cysteine at codon 2370 is highly conserved and computational algorithms (SIFT, PolyPhen2) predict this variant to be deleterious. Based on the above information, this variant is considered likely pathogenic. References: Mayo ADPKD variant database: http://pkdb.mayo.edu/ Audrezet M et al. Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2016 Mar;27(3):722-9. Bataille S et al. High Resolution Melt analysis for mutation screening in PKD1 and PKD2. BMC Nephrol. 2011; 12:57. Rossetti S et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet. 2003; 361(9376):2196-201. Rossetti S et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007 Jul;18(7):2143-60. |