SYNM : c.4154A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.4154A>G	p.E1385G (Glu > Gly)	substitution	missense	chr15:99672722 (forward strand)	0.49473231

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.49473231 (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	0.51347220 34264 / 66730	0.31871047 3124 / 9802	0.66221551 5703 / 8612	0.49073177 8101 / 16508	0.41038714 4749 / 11572	0.50302389 3327 / 6614	0.51670379 464 / 898	0.49473231 59732 / 120736
ESP	0.48860 4070 / 8330	0.31329 1240 / 3958						0.43213 5310 / 12288
1KG	0.53465 432 / 808	0.30333 401 / 1322	0.62798 633 / 1008	0.53374 522 / 978	0.47550 330 / 694	0.52525 104 / 198		0.48363 2422 / 5008

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

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

0.58242 106 / 182 British	0.30328 37 / 122 African-American	0.55914 104 / 186 Chinese Dai	0.49419 85 / 172 Bengali	0.44149 83 / 188 Colombian
0.58411 125 / 214 Iberian	0.33333 64 / 192 African-Caribbean	0.67476 139 / 206 Han, Beijing	0.50971 105 / 206 Gujarati Indian	0.47656 61 / 128 Mexican, LA
0.46262 99 / 214 Toscani	0.24242 48 / 198 Esan, Nigeria	0.61538 128 / 208 Japanese	0.56373 115 / 204 Indian Telugu	0.46471 79 / 170 Peruvian
0.51515 102 / 198 Utah Europeans	0.36283 82 / 226 Gambian	0.63636 126 / 198 Kinh, Vietnam	0.51042 98 / 192 Punjabi, Lahore	0.51442 107 / 208 Puerto Rican
	0.36364 72 / 198 Luhya, Kenya	0.64762 136 / 210 Southern Han	0.58333 119 / 204 Tamil
	0.30000 51 / 170 Mende
	0.21759 47 / 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	ENST00000336292	LRG_415t1	NM_145728.2
Protein	ENSP00000336775	LRG_415p1

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
LRT	MutationTaster	MutationAssessor	FATHMM
	polymorphism (auto)		damaging

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.