TTN : c.3601A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.3601A>G	p.K1201E (Lys > Glu)	substitution	missense	chr2:179644855 (reverse strand)	0.69444399

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.69444399 (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	0.86549936 57734 / 66706	0.46331600 4812 / 10386	0.19911401 1708 / 8578	0.57859653 9548 / 16502	0.37255411 4303 / 11550	0.81739788 5403 / 6610	0.75607064 685 / 906	0.69444399 84193 / 121238
ESP	0.87023 7484 / 8600	0.47072 2074 / 4406						0.73489 9558 / 13006
1KG	0.86510 699 / 808	0.40772 539 / 1322	0.21726 219 / 1008	0.54397 532 / 978	0.50865 353 / 694	0.82323 163 / 198		0.50020 2505 / 5008

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

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

0.85165 155 / 182 British	0.43443 53 / 122 African-American	0.22581 42 / 186 Chinese Dai	0.49419 85 / 172 Bengali	0.59043 111 / 188 Colombian
0.87383 187 / 214 Iberian	0.41146 79 / 192 African-Caribbean	0.22816 47 / 206 Han, Beijing	0.64078 132 / 206 Gujarati Indian	0.46875 60 / 128 Mexican, LA
0.87850 188 / 214 Toscani	0.34343 68 / 198 Esan, Nigeria	0.20192 42 / 208 Japanese	0.50000 102 / 204 Indian Telugu	0.20588 35 / 170 Peruvian
0.85354 169 / 198 Utah Europeans	0.39381 89 / 226 Gambian	0.23232 46 / 198 Kinh, Vietnam	0.54167 104 / 192 Punjabi, Lahore	0.70673 147 / 208 Puerto Rican
	0.46970 93 / 198 Luhya, Kenya	0.20000 42 / 210 Southern Han	0.53431 109 / 204 Tamil
	0.41176 70 / 170 Mende
	0.40278 87 / 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	moderately 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.