LIPI : c.1354G>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1354G>A	p.E452K (Glu > Lys)	substitution	missense	chr21:15516948 (reverse strand)	0.31933291

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.31933291 (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	0.34711381 22947 / 66108	0.54451919 5504 / 10108	0.05152225 440 / 8540	0.23264438 3827 / 16450	0.27848990 3172 / 11390	0.32905591 2154 / 6546	0.32150776 290 / 902	0.31933291 38334 / 120044
ESP	0.33791 2904 / 8594	0.53295 2345 / 4400						0.40396 5249 / 12994
1KG	0.33292 269 / 808	0.55371 732 / 1322	0.05258 53 / 1008	0.19836 194 / 978	0.40058 278 / 694	0.31818 63 / 198		0.31729 1589 / 5008

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

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

0.35165 64 / 182 British	0.54098 66 / 122 African-American	0.03763 7 / 186 Chinese Dai	0.14535 25 / 172 Bengali	0.43617 82 / 188 Colombian
0.29439 63 / 214 Iberian	0.60938 117 / 192 African-Caribbean	0.04369 9 / 206 Han, Beijing	0.23786 49 / 206 Gujarati Indian	0.30469 39 / 128 Mexican, LA
0.33178 71 / 214 Toscani	0.55556 110 / 198 Esan, Nigeria	0.07212 15 / 208 Japanese	0.24510 50 / 204 Indian Telugu	0.40000 68 / 170 Peruvian
0.35859 71 / 198 Utah Europeans	0.57965 131 / 226 Gambian	0.04545 9 / 198 Kinh, Vietnam	0.17708 34 / 192 Punjabi, Lahore	0.42788 89 / 208 Puerto Rican
	0.51010 101 / 198 Luhya, Kenya	0.06190 13 / 210 Southern Han	0.17647 36 / 204 Tamil
	0.48235 82 / 170 Mende
	0.57870 125 / 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	ENST00000344577		NM_198996.2
Protein	ENSP00000343331

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 12.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated	moderately conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
unknown	polymorphism (auto)	low impact	damaging

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.