HELZ2 : c.1013C>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1013C>T	p.S338L (Ser > Leu)	substitution	missense	chr20:62200576 (reverse strand)	0.21306303

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.21306303 (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	0.19639712 12265 / 62450	0.03849321 374 / 9716	0.55265643 4681 / 8470	0.31345988 3633 / 11590	0.10269691 1150 / 11198	0.20400788 1242 / 6088	0.19770408 155 / 784	0.21306303 23500 / 110296
ESP	0.18907 1626 / 8600	0.04614 203 / 4400						0.14069 1829 / 13000
1KG	0.19307 156 / 808	0.00908 12 / 1322	0.52976 534 / 1008	0.29448 288 / 978	0.09510 66 / 694	0.20202 40 / 198		0.21885 1096 / 5008

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

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

0.19780 36 / 182 British	0.04098 5 / 122 African-American	0.43011 80 / 186 Chinese Dai	0.33721 58 / 172 Bengali	0.13830 26 / 188 Colombian
0.14486 31 / 214 Iberian	0.03125 6 / 192 African-Caribbean	0.55340 114 / 206 Han, Beijing	0.22816 47 / 206 Gujarati Indian	0.09375 12 / 128 Mexican, LA
0.19626 42 / 214 Toscani	0.00000 0 / 198 Esan, Nigeria	0.59615 124 / 208 Japanese	0.31373 64 / 204 Indian Telugu	0.04706 8 / 170 Peruvian
0.23737 47 / 198 Utah Europeans	0.00000 0 / 226 Gambian	0.52020 103 / 198 Kinh, Vietnam	0.32292 62 / 192 Punjabi, Lahore	0.09615 20 / 208 Puerto Rican
	0.00505 1 / 198 Luhya, Kenya	0.53810 113 / 210 Southern Han	0.27941 57 / 204 Tamil
	0.00000 0 / 170 Mende
	0.00000 0 / 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 25% of algorithms have predicted that this variant will adversely affect protein function
damaging	moderately radical	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	low impact	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.