SYNE1 : c.24755G>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.24755G>C	p.G8252A (Gly > Ala)	substitution	missense	chr6:152469188 (reverse strand)	0.35921903

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.35921903 (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	0.32302727 21418 / 66304	0.44412107 4578 / 10308	0.29891943 2545 / 8514	0.41910426 6906 / 16478	0.52482208 6047 / 11522	0.22745217 1498 / 6586	0.37114537 337 / 908	0.35921903 43329 / 120620
ESP	0.33733 2901 / 8600	0.44439 1958 / 4406						0.37360 4859 / 13006
1KG	0.35396 286 / 808	0.45764 605 / 1322	0.29861 301 / 1008	0.41309 404 / 978	0.51153 355 / 694	0.24747 49 / 198		0.39936 2000 / 5008

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

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

0.31319 57 / 182 British	0.47541 58 / 122 African-American	0.33871 63 / 186 Chinese Dai	0.37791 65 / 172 Bengali	0.45745 86 / 188 Colombian
0.44393 95 / 214 Iberian	0.44271 85 / 192 African-Caribbean	0.27184 56 / 206 Han, Beijing	0.40777 84 / 206 Gujarati Indian	0.53125 68 / 128 Mexican, LA
0.37850 81 / 214 Toscani	0.42929 85 / 198 Esan, Nigeria	0.27404 57 / 208 Japanese	0.45098 92 / 204 Indian Telugu	0.55294 94 / 170 Peruvian
0.26768 53 / 198 Utah Europeans	0.52212 118 / 226 Gambian	0.32828 65 / 198 Kinh, Vietnam	0.40625 78 / 192 Punjabi, Lahore	0.51442 107 / 208 Puerto Rican
	0.38889 77 / 198 Luhya, Kenya	0.28571 60 / 210 Southern Han	0.41667 85 / 204 Tamil
	0.50588 86 / 170 Mende
	0.44444 96 / 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 12.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated	moderately conservative		benign
LRT	MutationTaster	MutationAssessor	FATHMM
deleterious	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.