TTN : c.26681C>T

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.26681C>Tp.P8894L (Pro > Leu)substitutionmissense chr2:179578704 (reverse strand)0.07510496

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.07510496 (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
ExAC0.02773745
1834 / 66120		0.15548718
1516 / 9750		0.02792772
238 / 8522		0.16691105
2732 / 16368		0.19356828
2197 / 11350		0.05880561
386 / 6564		0.08632287
77 / 892		0.07510496
8980 / 119566
ESP 0.02556
211 / 8256		 0.13959
531 / 3804		 0.06153
742 / 12060
1KG
 0.02723
22 / 808		 0.16490
218 / 1322		 0.02579
26 / 1008		 0.17587
172 / 978		 0.15274
106 / 694		 0.07071
14 / 198		 0.11142
558 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.03297
6 / 182
British
0.22131
27 / 122
African-American
0.04301
8 / 186
Chinese Dai
0.19767
34 / 172
Bengali
0.16489
31 / 188
Colombian
0.02336
5 / 214
Iberian
0.15625
30 / 192
African-Caribbean
0.01456
3 / 206
Han, Beijing
0.16505
34 / 206
Gujarati Indian
0.18750
24 / 128
Mexican, LA
0.02336
5 / 214
Toscani
0.17677
35 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.16667
34 / 204
Indian Telugu
0.22941
39 / 170
Peruvian
0.03030
6 / 198
Utah Europeans
0.18584
42 / 226
Gambian
0.06566
13 / 198
Kinh, Vietnam
0.14583
28 / 192
Punjabi, Lahore
0.05769
12 / 208
Puerto Rican
0.16162
32 / 198
Luhya, Kenya
0.00952
2 / 210
Southern Han
0.20588
42 / 204
Tamil
0.15882
27 / 170
Mende
0.11574
25 / 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) neutral 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.