TTN : c.107267T>C

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.107267T>Cp.V35756A (Val > Ala)substitutionmissense chr2:179393111 (reverse strand)0.04465902

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.04465902 (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
ExAC0.02158760
1437 / 66566		0.12661076
1238 / 9778		0.16639535
1431 / 8600		0.05172832
853 / 16490		0.03126628
360 / 11514		0.00272480
18 / 6606		0.04708520
42 / 892		0.04465902
5379 / 120446
ESP 0.02071
170 / 8210		 0.11877
443 / 3730		 0.05134
613 / 11940
1KG
 0.03837
31 / 808		 0.13540
179 / 1322		 0.17361
175 / 1008		 0.04806
47 / 978		 0.04035
28 / 694		 0.00505
1 / 198		 0.09205
461 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.03297
6 / 182
British
0.13115
16 / 122
African-American
0.14516
27 / 186
Chinese Dai
0.07558
13 / 172
Bengali
0.05319
10 / 188
Colombian
0.03738
8 / 214
Iberian
0.09375
18 / 192
African-Caribbean
0.19903
41 / 206
Han, Beijing
0.03398
7 / 206
Gujarati Indian
0.03906
5 / 128
Mexican, LA
0.07009
15 / 214
Toscani
0.13636
27 / 198
Esan, Nigeria
0.15865
33 / 208
Japanese
0.03431
7 / 204
Indian Telugu
0.02353
4 / 170
Peruvian
0.01010
2 / 198
Utah Europeans
0.17699
40 / 226
Gambian
0.18687
37 / 198
Kinh, Vietnam
0.05208
10 / 192
Punjabi, Lahore
0.04327
9 / 208
Puerto Rican
0.15657
31 / 198
Luhya, Kenya
0.17619
37 / 210
Southern Han
0.04902
10 / 204
Tamil
0.13529
23 / 170
Mende
0.11111
24 / 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_391t1NM_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 benign benign
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) low impact 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.