GAA : c.596A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.596A>G	p.H199R (His > Arg)	substitution	missense	chr17:78079597 (forward strand)	0.67455416

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.67455416 (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	0.74552561 49403 / 66266	0.54120720 5595 / 10338	0.52928190 4555 / 8606	0.66184131 10927 / 16510	0.45909012 5308 / 11562	0.76371628 5039 / 6598	0.71729490 647 / 902	0.67455416 81474 / 120782
ESP	0.73826 6349 / 8600	0.54426 2398 / 4406						0.67254 8747 / 13006
1KG	0.75248 608 / 808	0.52118 689 / 1322	0.54365 548 / 1008	0.65235 638 / 978	0.54179 376 / 694	0.75758 150 / 198		0.60084 3009 / 5008

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

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

0.75824 138 / 182 British	0.55738 68 / 122 African-American	0.43011 80 / 186 Chinese Dai	0.58721 101 / 172 Bengali	0.55319 104 / 188 Colombian
0.78037 167 / 214 Iberian	0.52083 100 / 192 African-Caribbean	0.59709 123 / 206 Han, Beijing	0.67476 139 / 206 Gujarati Indian	0.48438 62 / 128 Mexican, LA
0.77103 165 / 214 Toscani	0.47475 94 / 198 Esan, Nigeria	0.54808 114 / 208 Japanese	0.66667 136 / 204 Indian Telugu	0.44118 75 / 170 Peruvian
0.69697 138 / 198 Utah Europeans	0.57080 129 / 226 Gambian	0.57576 114 / 198 Kinh, Vietnam	0.66667 128 / 192 Punjabi, Lahore	0.64904 135 / 208 Puerto Rican
	0.54040 107 / 198 Luhya, Kenya	0.55714 117 / 210 Southern Han	0.65686 134 / 204 Tamil
	0.57647 98 / 170 Mende
	0.43056 93 / 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	ENST00000302262	LRG_673t1	NM_000152.3
Protein	ENSP00000305692	LRG_673p1		P10253

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.