TTN : c.88187T>C

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.88187T>Cp.I29396T (Ile > Thr)substitutionmissense chr2:179421694 (reverse strand)0.35060367

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.35060367 (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
ExAC0.22982562
15288 / 66520		0.54274638
5320 / 9802		0.69877098
5913 / 8462		0.52090656
8596 / 16502		0.42898172
4929 / 11490		0.27647951
1822 / 6590		0.33073497
297 / 898		0.35060367
42165 / 120264
ESP 0.22060
1831 / 8300		 0.52383
2066 / 3944		 0.31828
3897 / 12244
1KG
 0.23515
190 / 808		 0.56657
749 / 1322		 0.71528
721 / 1008		 0.55010
538 / 978		 0.40490
281 / 694		 0.30808
61 / 198		 0.50719
2540 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.23077
42 / 182
British
0.51639
63 / 122
African-American
0.83871
156 / 186
Chinese Dai
0.63372
109 / 172
Bengali
0.38830
73 / 188
Colombian
0.24299
52 / 214
Iberian
0.54688
105 / 192
African-Caribbean
0.65534
135 / 206
Han, Beijing
0.49029
101 / 206
Gujarati Indian
0.38281
49 / 128
Mexican, LA
0.26168
56 / 214
Toscani
0.63636
126 / 198
Esan, Nigeria
0.64423
134 / 208
Japanese
0.55882
114 / 204
Indian Telugu
0.51176
87 / 170
Peruvian
0.20202
40 / 198
Utah Europeans
0.56637
128 / 226
Gambian
0.73737
146 / 198
Kinh, Vietnam
0.53646
103 / 192
Punjabi, Lahore
0.34615
72 / 208
Puerto Rican
0.54040
107 / 198
Luhya, Kenya
0.71429
150 / 210
Southern Han
0.54412
111 / 204
Tamil
0.53529
91 / 170
Mende
0.59722
129 / 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.