SYNE1 : c.14830T>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.14830T>A	p.L4944M (Leu > Met)	substitution	missense	chr6:152647681 (reverse strand)	0.77974120

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.77974120 (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	0.75809015 50554 / 66686	0.93155162 9690 / 10402	0.83838150 7252 / 8650	0.64433802 10629 / 16496	0.87562619 10138 / 11578	0.85310136 5639 / 6610	0.77533040 704 / 908	0.77974120 94606 / 121330
ESP	0.74942 6445 / 8600	0.92964 4096 / 4406						0.81047 10541 / 13006
1KG	0.72401 585 / 808	0.95461 1262 / 1322	0.84921 856 / 1008	0.63804 624 / 978	0.84438 586 / 694	0.84343 167 / 198		0.81470 4080 / 5008

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

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

0.72527 132 / 182 British	0.91803 112 / 122 African-American	0.86559 161 / 186 Chinese Dai	0.66860 115 / 172 Bengali	0.83511 157 / 188 Colombian
0.67290 144 / 214 Iberian	0.93750 180 / 192 African-Caribbean	0.85922 177 / 206 Han, Beijing	0.65534 135 / 206 Gujarati Indian	0.85156 109 / 128 Mexican, LA
0.72897 156 / 214 Toscani	0.95455 189 / 198 Esan, Nigeria	0.87019 181 / 208 Japanese	0.61275 125 / 204 Indian Telugu	0.90588 154 / 170 Peruvian
0.77273 153 / 198 Utah Europeans	0.98230 222 / 226 Gambian	0.86869 172 / 198 Kinh, Vietnam	0.65104 125 / 192 Punjabi, Lahore	0.79808 166 / 208 Puerto Rican
	0.94444 187 / 198 Luhya, Kenya	0.78571 165 / 210 Southern Han	0.60784 124 / 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.