PLEC : c.4046A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.4046A>G	p.H1349R (His > Arg)	substitution	missense	chr8:145001031 (reverse strand)	0.41276773

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.41276773 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.42337136 27984 / 66098	0.83179865 8130 / 9774	0.14878731 1276 / 8576	0.36021571 5945 / 16504	0.26828423 3096 / 11540	0.41204965 2722 / 6606	0.42040359 375 / 892	0.41276773 49528 / 119990
ESP	0.42938 3666 / 8538	0.82277 3556 / 4322						0.56159 7222 / 12860
1KG	0.44554 360 / 808	0.87821 1161 / 1322	0.14286 144 / 1008	0.34765 340 / 978	0.36744 255 / 694	0.38889 77 / 198		0.46665 2337 / 5008

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

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

0.41758 76 / 182 British	0.79508 97 / 122 African-American	0.12366 23 / 186 Chinese Dai	0.34302 59 / 172 Bengali	0.43085 81 / 188 Colombian
0.46729 100 / 214 Iberian	0.86979 167 / 192 African-Caribbean	0.14563 30 / 206 Han, Beijing	0.35437 73 / 206 Gujarati Indian	0.25781 33 / 128 Mexican, LA
0.45794 98 / 214 Toscani	0.93434 185 / 198 Esan, Nigeria	0.17308 36 / 208 Japanese	0.33333 68 / 204 Indian Telugu	0.24118 41 / 170 Peruvian
0.43434 86 / 198 Utah Europeans	0.86283 195 / 226 Gambian	0.11111 22 / 198 Kinh, Vietnam	0.33333 64 / 192 Punjabi, Lahore	0.48077 100 / 208 Puerto Rican
	0.81818 162 / 198 Luhya, Kenya	0.15714 33 / 210 Southern Han	0.37255 76 / 204 Tamil
	0.90000 153 / 170 Mende
	0.93519 202 / 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	ENST00000436759		NM_000445.3
Protein	ENSP00000388180

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 0% of algorithms have predicted that this variant will adversely affect protein function
tolerated	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.