TTN : c.76343G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.76343G>Ap.S25448N (Ser > Asn)substitutionmissense chr2:179434516 (reverse strand)0.04127000

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.04127000 (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
ExAC0.02215247
1475 / 66584		0.07056781
691 / 9792		0.16987104
1449 / 8530		0.05176385
854 / 16498		0.02991304
344 / 11500		0.01732523
114 / 6580		0.04586130
41 / 894		0.04127000
4968 / 120378
ESP 0.02021
167 / 8262		 0.06396
241 / 3768		 0.03392
408 / 12030
1KG
 0.03837
31 / 808		 0.08548
113 / 1322		 0.17361
175 / 1008		 0.04806
47 / 978		 0.04179
29 / 694		 0.01010
2 / 198		 0.07927
397 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.03297
6 / 182
British
0.08197
10 / 122
African-American
0.13441
25 / 186
Chinese Dai
0.07558
13 / 172
Bengali
0.05319
10 / 188
Colombian
0.03738
8 / 214
Iberian
0.06250
12 / 192
African-Caribbean
0.21359
44 / 206
Han, Beijing
0.03398
7 / 206
Gujarati Indian
0.03906
5 / 128
Mexican, LA
0.07009
15 / 214
Toscani
0.08081
16 / 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
0.12832
29 / 226
Gambian
0.18687
37 / 198
Kinh, Vietnam
0.05208
10 / 192
Punjabi, Lahore
0.04808
10 / 208
Puerto Rican
0.08586
17 / 198
Luhya, Kenya
0.17143
36 / 210
Southern Han
0.04902
10 / 204
Tamil
0.10000
17 / 170
Mende
0.05556
12 / 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
25% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative possibly damaging 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.