TTN : c.31564A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.31564A>G	p.I10522V (Ile > Val)	substitution	missense	chr2:179558366 (reverse strand)	0.35363728

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.35363728 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

The role on non-truncating TTN variants in cardiac disease has not yet been analysed in these studies.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.24565407 15177 / 61782	0.56744529 5393 / 9504	0.57613365 4828 / 8380	0.50037903 7921 / 15830	0.44935897 4907 / 10920	0.26363348 1663 / 6308	0.32352941 275 / 850	0.35363728 40164 / 113574
ESP	0.22859 1858 / 8128	0.55887 2003 / 3584						0.32966 3861 / 11712
1KG	0.24381 197 / 808	0.58775 777 / 1322	0.56845 573 / 1008	0.51636 505 / 978	0.41931 291 / 694	0.25253 50 / 198		0.47784 2393 / 5008

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

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

0.25824 47 / 182 British	0.54918 67 / 122 African-American	0.67204 125 / 186 Chinese Dai	0.56977 98 / 172 Bengali	0.37234 70 / 188 Colombian
0.24299 52 / 214 Iberian	0.56250 108 / 192 African-Caribbean	0.50485 104 / 206 Han, Beijing	0.47573 98 / 206 Gujarati Indian	0.40625 52 / 128 Mexican, LA
0.25701 55 / 214 Toscani	0.66667 132 / 198 Esan, Nigeria	0.46635 97 / 208 Japanese	0.52451 107 / 204 Indian Telugu	0.54118 92 / 170 Peruvian
0.21717 43 / 198 Utah Europeans	0.58850 133 / 226 Gambian	0.61111 121 / 198 Kinh, Vietnam	0.50521 97 / 192 Punjabi, Lahore	0.37019 77 / 208 Puerto Rican
	0.55556 110 / 198 Luhya, Kenya	0.60000 126 / 210 Southern Han	0.51471 105 / 204 Tamil
	0.55294 94 / 170 Mende
	0.61574 133 / 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	ENST00000589042	LRG_391t1	NM_001267550.1
Protein	ENSP00000467141	LRG_391p1

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 12.5% of algorithms have predicted that this variant will adversely affect protein function
damaging	conservative
LRT	MutationTaster	MutationAssessor	FATHMM
	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.