Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Cavalleri Lab, |
RCV001095622 | SCV001251259 | uncertain significance | Polycystic kidney disease, adult type | 2020-02-05 | criteria provided, single submitter | research | PP3, PP4, PP5 |
Ce |
RCV001172091 | SCV001335034 | pathogenic | not provided | 2020-03-01 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV001172091 | SCV001475263 | likely pathogenic | not provided | 2022-12-20 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene, including a de novo case. This variant has been seen where an alternate explanation for disease was also identified, suggesting this variant may not cause disease. Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure. |
Gene |
RCV001172091 | SCV001794327 | uncertain significance | not provided | 2022-09-19 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); 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: 22383692, 21115670, 23431072, 22508176, 29338003, 31740684, 31056860, 33454723) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001095622 | SCV004803234 | likely pathogenic | Polycystic kidney disease, adult type | 2024-01-02 | criteria provided, single submitter | clinical testing | Variant summary: PKD1 c.7300C>T (p.Arg2434Trp) results in a non-conservative amino acid change located in the PKD/REJ-like domain (IPR002859) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.7300C>T has been reported in the literature in multiple individuals affected with Autosomal Dominant Polycystic Kidney Disease (examples, Wang_2019, Cornec-Le Gall_2013, Hoefele_2011, Yu_2022). Detailed clinical information, familial segregation and co-occurring evidence were not all provided. 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. The following publications have been ascertained in the context of this evaluation (PMID: 31056860, 23431072, 21115670, 35778421). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (Pathogenic/Likely Pathogenic, n=2; VUS, n=2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |