TTN : c.96158T>C

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.96158T>Cp.I32053T (Ile > Thr)substitutionmissense chr2:179408713 (reverse strand)0.08082230

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.08082230 (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
ExAC0.03427347
2287 / 66728		0.14521721
1424 / 9806		0.02553982
220 / 8614		0.18295785
3021 / 16512		0.20311419
2348 / 11560		0.05896583
390 / 6614		0.07555556
68 / 900		0.08082230
9758 / 120734
ESP 0.03217
268 / 8332		 0.15402
609 / 3954		 0.07138
877 / 12286
1KG
 0.04455
36 / 808		 0.14599
193 / 1322		 0.02579
26 / 1008		 0.19939
195 / 978		 0.16427
114 / 694		 0.08081
16 / 198		 0.11581
580 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.04945
9 / 182
British
0.12295
15 / 122
African-American
0.05376
10 / 186
Chinese Dai
0.20930
36 / 172
Bengali
0.16489
31 / 188
Colombian
0.03738
8 / 214
Iberian
0.18229
35 / 192
African-Caribbean
0.01456
3 / 206
Han, Beijing
0.19903
41 / 206
Gujarati Indian
0.17188
22 / 128
Mexican, LA
0.05140
11 / 214
Toscani
0.19697
39 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.21569
44 / 204
Indian Telugu
0.24706
42 / 170
Peruvian
0.04040
8 / 198
Utah Europeans
0.11947
27 / 226
Gambian
0.05051
10 / 198
Kinh, Vietnam
0.15625
30 / 192
Punjabi, Lahore
0.09135
19 / 208
Puerto Rican
0.16667
33 / 198
Luhya, Kenya
0.01429
3 / 210
Southern Han
0.21569
44 / 204
Tamil
0.08824
15 / 170
Mende
0.13426
29 / 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) 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.