LIPI : c.1395C>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1395C>A	p.D465E (Asp > Glu)	substitution	missense	chr21:15481365 (reverse strand)	0.50091480

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.50091480 (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	0.49280360 32870 / 66700	0.50124976 5214 / 10402	0.51248555 4433 / 8650	0.53223070 8785 / 16506	0.48382633 5594 / 11562	0.51754917 3421 / 6610	0.50991189 463 / 908	0.50091480 60780 / 121338
ESP	0.49430 4250 / 8598	0.50794 2238 / 4406						0.49892 6488 / 13004
1KG	0.49505 400 / 808	0.50303 665 / 1322	0.50992 514 / 1008	0.55215 540 / 978	0.54035 375 / 694	0.53030 105 / 198		0.51897 2599 / 5008

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

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

0.48901 89 / 182 British	0.51639 63 / 122 African-American	0.56989 106 / 186 Chinese Dai	0.53488 92 / 172 Bengali	0.50000 94 / 188 Colombian
0.55140 118 / 214 Iberian	0.46354 89 / 192 African-Caribbean	0.48058 99 / 206 Han, Beijing	0.52913 109 / 206 Gujarati Indian	0.54688 70 / 128 Mexican, LA
0.43458 93 / 214 Toscani	0.46970 93 / 198 Esan, Nigeria	0.45673 95 / 208 Japanese	0.55392 113 / 204 Indian Telugu	0.56471 96 / 170 Peruvian
0.50505 100 / 198 Utah Europeans	0.47788 108 / 226 Gambian	0.58586 116 / 198 Kinh, Vietnam	0.56771 109 / 192 Punjabi, Lahore	0.55288 115 / 208 Puerto Rican
	0.55051 109 / 198 Luhya, Kenya	0.46667 98 / 210 Southern Han	0.57353 117 / 204 Tamil
	0.58824 100 / 170 Mende
	0.47685 103 / 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	conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	neutral	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.