TTN : c.78674T>C

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.78674T>Cp.I26225T (Ile > Thr)substitutionmissense chr2:179432185 (reverse strand)0.23680490

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.23680490 (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
ExAC0.30126202
20052 / 66560		0.04705042
461 / 9798		0.04443142
379 / 8530		0.22009306
3595 / 16334		0.09803751
1129 / 11516		0.39821266
2629 / 6602		0.25391499
227 / 894		0.23680490
28472 / 120234
ESP 0.30296
2480 / 8186		 0.05435
200 / 3680		 0.22586
2680 / 11866
1KG
 0.29827
241 / 808		 0.00530
7 / 1322		 0.04266
43 / 1008		 0.21677
212 / 978		 0.11239
78 / 694		 0.35354
70 / 198		 0.12999
651 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.33516
61 / 182
British
0.04098
5 / 122
African-American
0.03763
7 / 186
Chinese Dai
0.20930
36 / 172
Bengali
0.16489
31 / 188
Colombian
0.27570
59 / 214
Iberian
0.00521
1 / 192
African-Caribbean
0.04369
9 / 206
Han, Beijing
0.26699
55 / 206
Gujarati Indian
0.11719
15 / 128
Mexican, LA
0.24299
52 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.03846
8 / 208
Japanese
0.17647
36 / 204
Indian Telugu
0.03529
6 / 170
Peruvian
0.34848
69 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.05051
10 / 198
Kinh, Vietnam
0.20312
39 / 192
Punjabi, Lahore
0.12500
26 / 208
Puerto Rican
0.00505
1 / 198
Luhya, Kenya
0.04286
9 / 210
Southern Han
0.22549
46 / 204
Tamil
0.00000
0 / 170
Mende
0.00000
0 / 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
37.5% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative possibly damaging benign
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) medium 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.