SYNM : c.812T>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.812T>C	p.V271A (Val > Ala)	substitution	missense	chr15:99653800 (forward strand)	0.58909306

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.58909306 (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	0.60265790 39045 / 64788	0.46128200 4289 / 9298	0.70939661 5949 / 8386	0.59595643 9521 / 15976	0.50871776 5602 / 11012	0.59510533 3842 / 6456	0.63188073 551 / 872	0.58909306 68799 / 116788
ESP	0.58032 4884 / 8416	0.47384 1974 / 4166						0.54506 6858 / 12582
1KG	0.61881 500 / 808	0.44402 587 / 1322	0.69444 700 / 1008	0.60941 596 / 978	0.54323 377 / 694	0.59596 118 / 198		0.57468 2878 / 5008

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

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

0.63736 116 / 182 British	0.47541 58 / 122 African-American	0.62366 116 / 186 Chinese Dai	0.58140 100 / 172 Bengali	0.50532 95 / 188 Colombian
0.64486 138 / 214 Iberian	0.46875 90 / 192 African-Caribbean	0.72816 150 / 206 Han, Beijing	0.58252 120 / 206 Gujarati Indian	0.50781 65 / 128 Mexican, LA
0.60748 130 / 214 Toscani	0.30808 61 / 198 Esan, Nigeria	0.70192 146 / 208 Japanese	0.64216 131 / 204 Indian Telugu	0.54706 93 / 170 Peruvian
0.58586 116 / 198 Utah Europeans	0.50885 115 / 226 Gambian	0.70202 139 / 198 Kinh, Vietnam	0.56771 109 / 192 Punjabi, Lahore	0.59615 124 / 208 Puerto Rican
	0.46970 93 / 198 Luhya, Kenya	0.70952 149 / 210 Southern Han	0.66667 136 / 204 Tamil
	0.49412 84 / 170 Mende
	0.39815 86 / 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	benign	benign
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.