SYNE1 : c.12149A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.12149A>G	p.K4050R (Lys > Arg)	substitution	missense	chr6:152658142 (reverse strand)	0.75468099

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.75468099 (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	0.74776427 49333 / 65974	0.92812983 9608 / 10352	0.85444965 7297 / 8540	0.62114000 10178 / 16386	0.70575260 7999 / 11334	0.83683090 5503 / 6576	0.76726058 689 / 898	0.75468099 90607 / 120060
ESP	0.71942 6187 / 8600	0.92238 4064 / 4406						0.78818 10251 / 13006
1KG	0.71535 578 / 808	0.95688 1265 / 1322	0.86310 870 / 1008	0.60838 595 / 978	0.71470 496 / 694	0.84848 168 / 198		0.79313 3972 / 5008

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

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

0.69780 127 / 182 British	0.91803 112 / 122 African-American	0.87634 163 / 186 Chinese Dai	0.62209 107 / 172 Bengali	0.76064 143 / 188 Colombian
0.69159 148 / 214 Iberian	0.93229 179 / 192 African-Caribbean	0.87379 180 / 206 Han, Beijing	0.62621 129 / 206 Gujarati Indian	0.60156 77 / 128 Mexican, LA
0.71963 154 / 214 Toscani	0.94949 188 / 198 Esan, Nigeria	0.87019 181 / 208 Japanese	0.58824 120 / 204 Indian Telugu	0.66471 113 / 170 Peruvian
0.75253 149 / 198 Utah Europeans	0.98230 222 / 226 Gambian	0.88889 176 / 198 Kinh, Vietnam	0.61979 119 / 192 Punjabi, Lahore	0.78365 163 / 208 Puerto Rican
	0.96970 192 / 198 Luhya, Kenya	0.80952 170 / 210 Southern Han	0.58824 120 / 204 Tamil
	0.95882 163 / 170 Mende
	0.96759 209 / 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.