Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000516396 | SCV000614457 | uncertain significance | not specified | 2016-09-30 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000764033 | SCV000894987 | uncertain significance | Polycystic kidney disease, adult type | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002469179 | SCV002765713 | uncertain significance | not provided | 2022-12-12 | criteria provided, single submitter | clinical testing | Identified in unrelated patients with polycystic kidney disease in published literature (Bataille et al., 2011; Chang et al., 2013; Cornec-Le Gall et al., 2013); 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: 23431072, 22008521, 23985799, 29801666, 31514750) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000516396 | SCV003934668 | uncertain significance | not specified | 2023-05-26 | criteria provided, single submitter | clinical testing | Variant summary: PKD1 c.10043G>A (p.Arg3348Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 186804 control chromosomes, predominantly at a frequency of 0.00052 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in PKD1 causing Polycystic Kidney Disease 1 phenotype (0.0005), suggesting that the variant could be a benign polymorphism found primarily in populations of Non-Finnish European origin, yet this should be interpreted with caution due to the presence of the PKD1 pseudogene. c.10043G>A has been reported in the literature in multiple individuals affected with Polycystic Kidney Disease 1 (e.g. Bataille_2011, Chang_2013, Cornec-LeGall_2013, Carrera_2016, Bullich_2018). However, this also includes cases where it was found in individuals with other PKD1 variants, including a truncating variant (PKD1 c.1960C>T, p.Arg654X; Chang_2013) and a pathogenic variant in PKD2 (PKD2 c.1094+1G>A; Carrera_2016), providing supporting evidence for a benign role. Thus, these reports do not provide unequivocal conclusions about association of the variant with Polycystic Kidney Disease 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26139440, 22008521, 29801666, 27499327, 23985799, 23431072). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |