Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002485575 | SCV002789284 | pathogenic | Polycystic kidney disease, adult type | 2022-01-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002485575 | SCV003844775 | pathogenic | Polycystic kidney disease, adult type | 2023-02-15 | criteria provided, single submitter | clinical testing | Variant summary: PKD1 c.755dupC (p.Pro253AlafsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.4e-05 in 138012 control chromosomes (gnomAD), however quality metrics indicate this data should be interpreted with caution. c.755dupC has been reported in the literature in individuals affected with Polycystic Kidney Disease, including one family in which the variant segregated with disease (e.g. Petrola_2005, Groopman_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Prevention |
RCV003392519 | SCV004121280 | pathogenic | PKD1-related condition | 2023-10-13 | criteria provided, single submitter | clinical testing | The PKD1 c.755dupC variant is predicted to result in a frameshift and premature protein termination (p.Pro253Alafs*8). This variant has been reported to be pathogenic for autosomal dominant polycystic kidney disease (ADPKD) (see for example at Groopman et al. 2018. PubMed ID: 30586318, Table S7). This variant is reported in 0.016% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2168237-C-CG). Frameshift variants in PKD1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
| Gharavi Laboratory, |
RCV000681732 | SCV000809187 | pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |