TTN : c.71993G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.71993G>Ap.R23998H (Arg > His)substitutionmissense chr2:179438866 (reverse strand)0.07443806

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.07443806 (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
ExAC0.03261783
2173 / 66620		0.08026961
786 / 9792		0.02587626
220 / 8502		0.18197238
3004 / 16508		0.20192308
2331 / 11544		0.05898367
390 / 6612		0.07126949
64 / 898		0.07443806
8968 / 120476
ESP 0.02918
243 / 8328		 0.08708
345 / 3962		 0.04784
588 / 12290
1KG
 0.03837
31 / 808		 0.08775
116 / 1322		 0.02579
26 / 1008		 0.19836
194 / 978		 0.15418
107 / 694		 0.08081
16 / 198		 0.09784
490 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.04396
8 / 182
British
0.05738
7 / 122
African-American
0.05376
10 / 186
Chinese Dai
0.20349
35 / 172
Bengali
0.14894
28 / 188
Colombian
0.03271
7 / 214
Iberian
0.13542
26 / 192
African-Caribbean
0.01456
3 / 206
Han, Beijing
0.19903
41 / 206
Gujarati Indian
0.17188
22 / 128
Mexican, LA
0.04206
9 / 214
Toscani
0.10101
20 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.21569
44 / 204
Indian Telugu
0.24118
41 / 170
Peruvian
0.03535
7 / 198
Utah Europeans
0.07965
18 / 226
Gambian
0.05051
10 / 198
Kinh, Vietnam
0.15625
30 / 192
Punjabi, Lahore
0.07692
16 / 208
Puerto Rican
0.10101
20 / 198
Luhya, Kenya
0.01429
3 / 210
Southern Han
0.21569
44 / 204
Tamil
0.06471
11 / 170
Mende
0.06481
14 / 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 conservative probably damaging probably damaging
LRT MutationTaster MutationAssessor FATHMM
disease-causing high 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.