NOS3 : c.894T>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.894T>G	p.D298E (Asp > Glu)	substitution	missense	chr7:150696111 (forward strand)	0.75301506

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.75301506 (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	0.68618825 44922 / 65466	0.89056714 9139 / 10262	0.89656373 7723 / 8614	0.82260996 13578 / 16506	0.83108225 9599 / 11550	0.70786687 4679 / 6610	0.72471910 645 / 890	0.75301506 90285 / 119898
ESP	0.67587 5803 / 8586	0.88448 3897 / 4406						0.74661 9700 / 12992
1KG	0.62871 508 / 808	0.92965 1229 / 1322	0.87004 877 / 1008	0.83231 814 / 978	0.78530 545 / 694	0.76768 152 / 198		0.82368 4125 / 5008

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

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

0.66484 121 / 182 British	0.89344 109 / 122 African-American	0.87097 162 / 186 Chinese Dai	0.84302 145 / 172 Bengali	0.73404 138 / 188 Colombian
0.61682 132 / 214 Iberian	0.91667 176 / 192 African-Caribbean	0.86408 178 / 206 Han, Beijing	0.85437 176 / 206 Gujarati Indian	0.80469 103 / 128 Mexican, LA
0.60280 129 / 214 Toscani	0.89899 178 / 198 Esan, Nigeria	0.91827 191 / 208 Japanese	0.79412 162 / 204 Indian Telugu	0.91176 155 / 170 Peruvian
0.63636 126 / 198 Utah Europeans	0.92478 209 / 226 Gambian	0.84343 167 / 198 Kinh, Vietnam	0.84896 163 / 192 Punjabi, Lahore	0.71635 149 / 208 Puerto Rican
	0.96465 191 / 198 Luhya, Kenya	0.85238 179 / 210 Southern Han	0.82353 168 / 204 Tamil
	0.95294 162 / 170 Mende
	0.94444 204 / 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	ENST00000297494		NM_000603.4
Protein	ENSP00000297494			P29474

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
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)		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.