TTN : c.24431A>C

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.24431A>Cp.E8144A (Glu > Ala)substitutionmissense chr2:179583496 (reverse strand)0.17662534

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.17662534 (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
ExAC0.14541934
9689 / 66628		0.15015322
1470 / 9790		0.42707118
3660 / 8570		0.22450588
3703 / 16494		0.17367141
2000 / 11516		0.09406241
621 / 6602		0.15590200
140 / 898		0.17662534
21283 / 120498
ESP 0.15165
1266 / 8348		 0.14854
590 / 3972		 0.15065
1856 / 12320
1KG
 0.17327
140 / 808		 0.17322
229 / 1322		 0.43750
441 / 1008		 0.24642
241 / 978		 0.18300
127 / 694		 0.09091
18 / 198		 0.23882
1196 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.20879
38 / 182
British
0.17213
21 / 122
African-American
0.51075
95 / 186
Chinese Dai
0.25000
43 / 172
Bengali
0.18085
34 / 188
Colombian
0.16822
36 / 214
Iberian
0.15625
30 / 192
African-Caribbean
0.39320
81 / 206
Han, Beijing
0.21845
45 / 206
Gujarati Indian
0.12500
16 / 128
Mexican, LA
0.18692
40 / 214
Toscani
0.15152
30 / 198
Esan, Nigeria
0.38462
80 / 208
Japanese
0.25980
53 / 204
Indian Telugu
0.20000
34 / 170
Peruvian
0.13131
26 / 198
Utah Europeans
0.18584
42 / 226
Gambian
0.44444
88 / 198
Kinh, Vietnam
0.24479
47 / 192
Punjabi, Lahore
0.20673
43 / 208
Puerto Rican
0.16162
32 / 198
Luhya, Kenya
0.46190
97 / 210
Southern Han
0.25980
53 / 204
Tamil
0.20588
35 / 170
Mende
0.18056
39 / 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 moderately radical benign benign
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) low 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.