TTN : c.36625G>T

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.36625G>Tp.V12209L (Val > Leu)substitutionmissense chr2:179528068 (reverse strand)0.02690832

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.02690832 (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
ExAC0.00622618
392 / 62960		0.02212697
191 / 8632		0.23108790
1283 / 5552		0.05845791
743 / 12710		0.00645366
61 / 9452		0.02755398
171 / 6206		0.02463054
20 / 812		0.02690832
2861 / 106324
ESP 0.00455
18 / 3960		 0.02260
39 / 1726
57 / 5686
1KG
 0.00371
3 / 808		 0.02723
36 / 1322		 0.17163
173 / 1008		 0.06135
60 / 978		 0.01441
10 / 694		 0.03030
6 / 198		 0.05751
288 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.00000
0 / 182
British
0.02459
3 / 122
African-American
0.19355
36 / 186
Chinese Dai
0.10465
18 / 172
Bengali
0.03723
7 / 188
Colombian
0.00000
0 / 214
Iberian
0.03125
6 / 192
African-Caribbean
0.15534
32 / 206
Han, Beijing
0.04369
9 / 206
Gujarati Indian
0.00781
1 / 128
Mexican, LA
0.00935
2 / 214
Toscani
0.01515
3 / 198
Esan, Nigeria
0.19231
40 / 208
Japanese
0.05392
11 / 204
Indian Telugu
0.00588
1 / 170
Peruvian
0.00505
1 / 198
Utah Europeans
0.04867
11 / 226
Gambian
0.15657
31 / 198
Kinh, Vietnam
0.05208
10 / 192
Punjabi, Lahore
0.00481
1 / 208
Puerto Rican
0.01515
3 / 198
Luhya, Kenya
0.16190
34 / 210
Southern Han
0.05882
12 / 204
Tamil
0.04706
8 / 170
Mende
0.00926
2 / 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
tolerated conservative possibly damaging possibly damaging
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto)


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.