HELZ2 : c.3922G>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.3922G>T	p.V1308L (Val > Leu)	substitution	missense	chr20:62196253 (reverse strand)	0.39634476

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.39634476 (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	0.42304828 27268 / 64456	0.45169034 4516 / 9998	0.14638427 1251 / 8546	0.41148180 6759 / 16426	0.39641052 4550 / 11478	0.33476395 2184 / 6524	0.41244240 358 / 868	0.39634476 46886 / 118296
ESP	0.42643 3663 / 8590	0.43835 1927 / 4396						0.43046 5590 / 12986
1KG	0.43069 348 / 808	0.46445 614 / 1322	0.15873 160 / 1008	0.37730 369 / 978	0.38761 269 / 694	0.32828 65 / 198		0.36442 1825 / 5008

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

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

0.45604 83 / 182 British	0.42623 52 / 122 African-American	0.13441 25 / 186 Chinese Dai	0.37791 65 / 172 Bengali	0.37234 70 / 188 Colombian
0.46729 100 / 214 Iberian	0.42708 82 / 192 African-Caribbean	0.17961 37 / 206 Han, Beijing	0.37864 78 / 206 Gujarati Indian	0.40625 52 / 128 Mexican, LA
0.40187 86 / 214 Toscani	0.40404 80 / 198 Esan, Nigeria	0.17308 36 / 208 Japanese	0.36765 75 / 204 Indian Telugu	0.40000 68 / 170 Peruvian
0.39899 79 / 198 Utah Europeans	0.42920 97 / 226 Gambian	0.10606 21 / 198 Kinh, Vietnam	0.39583 76 / 192 Punjabi, Lahore	0.37981 79 / 208 Puerto Rican
	0.55051 109 / 198 Luhya, Kenya	0.19524 41 / 210 Southern Han	0.36765 75 / 204 Tamil
	0.53529 91 / 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	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.