HELZ2 : c.3368A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.3368A>G	p.H1123R (His > Arg)	substitution	missense	chr20:62196807 (reverse strand)	0.96640263

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.96640263 (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	0.95314208 57545 / 60374	0.99145799 8473 / 8546	0.99939335 8237 / 8242	0.99717999 16266 / 16312	0.98607392 11046 / 11202	0.89677419 5282 / 5890	0.96930946 758 / 782	0.96640263 107607 / 111348
ESP	0.95256 8133 / 8538	0.98891 4280 / 4328						0.96479 12413 / 12866
1KG	0.94802 766 / 808	0.99697 1318 / 1322	1.00000 1008 / 1008	1.00000 978 / 978	0.97118 674 / 694	0.91919 182 / 198		0.98363 4926 / 5008

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

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

0.95055 173 / 182 British	0.97541 119 / 122 African-American	1.00000 186 / 186 Chinese Dai	1.00000 172 / 172 Bengali	0.97872 184 / 188 Colombian
0.95794 205 / 214 Iberian	0.99479 191 / 192 African-Caribbean	1.00000 206 / 206 Han, Beijing	1.00000 206 / 206 Gujarati Indian	0.96875 124 / 128 Mexican, LA
0.95794 205 / 214 Toscani	1.00000 198 / 198 Esan, Nigeria	1.00000 208 / 208 Japanese	1.00000 204 / 204 Indian Telugu	0.98235 167 / 170 Peruvian
0.92424 183 / 198 Utah Europeans	1.00000 226 / 226 Gambian	1.00000 198 / 198 Kinh, Vietnam	1.00000 192 / 192 Punjabi, Lahore	0.95673 199 / 208 Puerto Rican
	1.00000 198 / 198 Luhya, Kenya	1.00000 210 / 210 Southern Han	1.00000 204 / 204 Tamil
	1.00000 170 / 170 Mende
	1.00000 216 / 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	ENST00000467148		NM_001037335.2
Protein	ENSP00000417401			Q9BYK8

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.