TTN : c.20861C>T

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.20861C>Tp.A6954V (Ala > Val)substitutionmissense chr2:179589241 (reverse strand)0.05105354

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.05105354 (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
ExAC0.01978335
1293 / 65358		0.00692292
67 / 9678		0.00082840
7 / 8450		0.13900527
2057 / 14798		0.18727946
2123 / 11336		0.05620037
368 / 6548		0.06928406
60 / 866		0.05105354
5975 / 117034
ESP 0.01902
158 / 8308		 0.00710
28 / 3944		 0.01518
186 / 12252
1KG
 0.02104
17 / 808		 0.00227
3 / 1322		 0.00198
2 / 1008		 0.12577
123 / 978		 0.14409
100 / 694		 0.06566
13 / 198		 0.05152
258 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.02198
4 / 182
British
0.00820
1 / 122
African-American
0.00538
1 / 186
Chinese Dai
0.14535
25 / 172
Bengali
0.14894
28 / 188
Colombian
0.01869
4 / 214
Iberian
0.01042
2 / 192
African-Caribbean
0.00000
0 / 206
Han, Beijing
0.12136
25 / 206
Gujarati Indian
0.17969
23 / 128
Mexican, LA
0.01402
3 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.14216
29 / 204
Indian Telugu
0.24706
42 / 170
Peruvian
0.03030
6 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.00505
1 / 198
Kinh, Vietnam
0.09375
18 / 192
Punjabi, Lahore
0.03365
7 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.00000
0 / 210
Southern Han
0.12745
26 / 204
Tamil
0.00000
0 / 170
Mende
0.00000
0 / 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
50% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative possibly damaging possibly damaging
LRT MutationTaster MutationAssessor FATHMM
disease-causing 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.