TTN : c.11252G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.11252G>Ap.G3751D (Gly > Asp)substitutionmissense chr2:179620951 (reverse strand)0.85080113

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.85080113 (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
ExAC0.92737640
61639 / 66466		0.83720930
8208 / 9804		0.75267691
6467 / 8592		0.79527061
12578 / 15816		0.54945341
6333 / 11526		0.88490623
5851 / 6612		0.86516854
770 / 890		0.85080113
101846 / 119706
ESP 0.93205
7723 / 8286		 0.84045
3266 / 3886		 0.90281
10989 / 12172
1KG
 0.92327
746 / 808		 0.82980
1097 / 1322		 0.77579
782 / 1008		 0.78221
765 / 978		 0.67003
465 / 694		 0.87879
174 / 198		 0.80451
4029 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.92857
169 / 182
British
0.77869
95 / 122
African-American
0.81183
151 / 186
Chinese Dai
0.75000
129 / 172
Bengali
0.75000
141 / 188
Colombian
0.92523
198 / 214
Iberian
0.83333
160 / 192
African-Caribbean
0.74757
154 / 206
Han, Beijing
0.82524
170 / 206
Gujarati Indian
0.64062
82 / 128
Mexican, LA
0.94393
202 / 214
Toscani
0.80808
160 / 198
Esan, Nigeria
0.76442
159 / 208
Japanese
0.77941
159 / 204
Indian Telugu
0.35882
61 / 170
Peruvian
0.89394
177 / 198
Utah Europeans
0.80973
183 / 226
Gambian
0.80808
160 / 198
Kinh, Vietnam
0.78125
150 / 192
Punjabi, Lahore
0.87019
181 / 208
Puerto Rican
0.85354
169 / 198
Luhya, Kenya
0.75238
158 / 210
Southern Han
0.76961
157 / 204
Tamil
0.83529
142 / 170
Mende
0.87037
188 / 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
12.5% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative benign benign
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) 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.