TTN : c.7174G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.7174G>Ap.G2392S (Gly > Ser)substitutionmissense chr2:179638721 (reverse strand)0.06532025

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.06532025 (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
ExAC0.02476316
1652 / 66712		0.09515571
990 / 10404		0.01787372
154 / 8616		0.15023019
2480 / 16508		0.19090909
2205 / 11550		0.05747126
380 / 6612		0.06938326
63 / 908		0.06532025
7924 / 121310
ESP 0.02209
190 / 8600		 0.09510
419 / 4406		 0.04682
609 / 13006
1KG
 0.02723
22 / 808		 0.09153
121 / 1322		 0.01488
15 / 1008		 0.15849
155 / 978		 0.15994
111 / 694		 0.07071
14 / 198		 0.08746
438 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.02747
5 / 182
British
0.15574
19 / 122
African-American
0.02151
4 / 186
Chinese Dai
0.16860
29 / 172
Bengali
0.15426
29 / 188
Colombian
0.03271
7 / 214
Iberian
0.08854
17 / 192
African-Caribbean
0.01456
3 / 206
Han, Beijing
0.15534
32 / 206
Gujarati Indian
0.20312
26 / 128
Mexican, LA
0.02336
5 / 214
Toscani
0.08081
16 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.17157
35 / 204
Indian Telugu
0.25882
44 / 170
Peruvian
0.02525
5 / 198
Utah Europeans
0.10177
23 / 226
Gambian
0.03030
6 / 198
Kinh, Vietnam
0.11979
23 / 192
Punjabi, Lahore
0.05769
12 / 208
Puerto Rican
0.07071
14 / 198
Luhya, Kenya
0.00952
2 / 210
Southern Han
0.17647
36 / 204
Tamil
0.09412
16 / 170
Mende
0.07407
16 / 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
62.5% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative probably damaging possibly damaging
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) medium impact damaging


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.