SYNE1 : c.11967G>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.11967G>T	p.E3989D (Glu > Asp)	substitution	missense	chr6:152665261 (reverse strand)	0.57614928

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.57614928 (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	0.60311395 40247 / 66732	0.44714588 4653 / 10406	0.64193100 5545 / 8638	0.51181102 8450 / 16510	0.59695817 6908 / 11572	0.54520714 3606 / 6614	0.57709251 524 / 908	0.57614928 69933 / 121380
ESP	0.61779 5313 / 8600	0.46868 2065 / 4406						0.56728 7378 / 13006
1KG	0.60767 491 / 808	0.41377 547 / 1322	0.64881 654 / 1008	0.50716 496 / 978	0.61816 429 / 694	0.58081 115 / 198		0.54553 2732 / 5008

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

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

0.58791 107 / 182 British	0.51639 63 / 122 African-American	0.66667 124 / 186 Chinese Dai	0.50000 86 / 172 Bengali	0.63830 120 / 188 Colombian
0.61682 132 / 214 Iberian	0.46354 89 / 192 African-Caribbean	0.65049 134 / 206 Han, Beijing	0.52913 109 / 206 Gujarati Indian	0.54688 70 / 128 Mexican, LA
0.60280 129 / 214 Toscani	0.42424 84 / 198 Esan, Nigeria	0.65385 136 / 208 Japanese	0.49020 100 / 204 Indian Telugu	0.61176 104 / 170 Peruvian
0.62121 123 / 198 Utah Europeans	0.32301 73 / 226 Gambian	0.63636 126 / 198 Kinh, Vietnam	0.56771 109 / 192 Punjabi, Lahore	0.64904 135 / 208 Puerto Rican
	0.33333 66 / 198 Luhya, Kenya	0.63810 134 / 210 Southern Han	0.45098 92 / 204 Tamil
	0.42353 72 / 170 Mende
	0.46296 100 / 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	ENST00000423061	LRG_427t2	NM_033071.3
Protein	ENSP00000396024	LRG_427p2

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.