|Variant (CDS)||Variant (protein)||Variant Type||Variant Effect||Genomic Location (GRCh37)||ExAC Frequency|
|c.1237C>T||p.R413X||substitution||nonsense||chr12:33003841 (reverse strand)||0.00001647|
This variant is considered a rare variant, with a population frequency of 0.00001647 (ExAC mean allelic frequency).
There is no significant excess of rare PKP2 Truncating variants in DCM (details).
OMGL: Detected in 0 / 304 DCM patients.
LMM: Detected in 0 / 123 DCM patients.
Rare PKP2 Truncating variants are significantly enriched in ARVC (details) and have an etiological fraction (EF) of 1.00.
OMGL: Detected in 2 / 361 ARVC patients - classified as Class 5-Certainly pathogenic.
The EF is the estimated proportion of rare variants of this class that will be pathogenic in a cardiomyopathy proband, a prior probability based solely on variant frequency data in cases and controls, and should be further refined by additional evidence such as family segregation data, known association with disease, population frequency, protein domain analysis, functional studies and in silico algorithms to assess the significance of a variant.
For more information on the clinical significance of this variant, please see the ClinVar entry.
|Database||European||African||East Asian||South Asian||American||Finnish||Other||Total|
0 / 66738
1 / 10404
0 / 8654
1 / 16512
0 / 11578
0 / 6614
0 / 908
2 / 121408
0 / 8600
1 / 4406
1 / 13006
0 / 1006
0 / 1322
0 / 1008
0 / 978
0 / 694
0 / 198
0 / 5008
The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).
1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.
2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.
3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL.
Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.
Genet Med. 2015 Nov;17(11):880-8.