PKP2 : c.1097T>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1097T>C	p.L366P (Leu > Pro)	substitution	missense	chr12:33021934 (reverse strand)	0.18002142

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.18002142 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM	OMGL: Detected in 0 / 304 DCM patients. LMM: Detected in 0 / 123 DCM patients.
ARVC	OMGL: Detected in 0 / 361 ARVC patients sequenced at OMGL.

DCM

OMGL: Detected in 0 / 304 DCM patients.

LMM: Detected in 0 / 123 DCM patients.

ARVC

OMGL: Detected in 0 / 361 ARVC patients sequenced at OMGL.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.20988820 14005 / 66726	0.19809689 2061 / 10404	0.02972473 257 / 8646	0.16327519 2696 / 16512	0.11873488 1374 / 11572	0.19207502 1270 / 6612	0.20704846 188 / 908	0.18002142 21851 / 121380
ESP	0.23012 1979 / 8600	0.20041 883 / 4406						0.22005 2862 / 13006
1KG	0.22649 183 / 808	0.21029 278 / 1322	0.03075 31 / 1008	0.12270 120 / 978	0.16138 112 / 694	0.17172 34 / 198		0.15136 758 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.21978 40 / 182 British	0.18033 22 / 122 African-American	0.03226 6 / 186 Chinese Dai	0.08140 14 / 172 Bengali	0.14894 28 / 188 Colombian
0.25701 55 / 214 Iberian	0.23438 45 / 192 African-Caribbean	0.04854 10 / 206 Han, Beijing	0.12136 25 / 206 Gujarati Indian	0.11719 15 / 128 Mexican, LA
0.17290 37 / 214 Toscani	0.18182 36 / 198 Esan, Nigeria	0.02404 5 / 208 Japanese	0.13725 28 / 204 Indian Telugu	0.17059 29 / 170 Peruvian
0.25758 51 / 198 Utah Europeans	0.20796 47 / 226 Gambian	0.03030 6 / 198 Kinh, Vietnam	0.16146 31 / 192 Punjabi, Lahore	0.19231 40 / 208 Puerto Rican
	0.19192 38 / 198 Luhya, Kenya	0.01905 4 / 210 Southern Han	0.10784 22 / 204 Tamil
	0.26471 45 / 170 Mende
	0.20833 45 / 216 Yoruba, Nigeria

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).

Other Variant & Gene Details

Canonical Sequences
Transcript	ENST00000070846	LRG_398t1	NM_004572.3
Protein	ENSP00000070846	LRG_398p1		Q99959

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 0% of algorithms have predicted that this variant will adversely affect protein function
tolerated	moderately conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	neutral	tolerated

References

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.