TTN : c.25274G>A

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.25274G>Ap.S8425N (Ser > Asn)substitutionmissense chr2:179582327 (reverse strand)0.17836272

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.17836272 (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
ExAC0.14611404
9543 / 65312
0.16611157
1596 / 9608
0.42644231
3548 / 8320
0.22572696
3664 / 16232
0.17562980
1966 / 11194
0.09285933
606 / 6526
0.15532880
137 / 882
0.17836272
21060 / 118074
ESP 0.15077
1242 / 8238
0.16295
613 / 3762
0.15458
1855 / 12000
1KG
0.17327
140 / 808
0.19365
256 / 1322
0.43552
439 / 1008
0.24642
241 / 978
0.18300
127 / 694
0.09091
18 / 198
0.24381
1221 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.20879
38 / 182
British
0.18033
22 / 122
African-American
0.50538
94 / 186
Chinese Dai
0.25000
43 / 172
Bengali
0.18085
34 / 188
Colombian
0.16822
36 / 214
Iberian
0.17188
33 / 192
African-Caribbean
0.39320
81 / 206
Han, Beijing
0.21845
45 / 206
Gujarati Indian
0.13281
17 / 128
Mexican, LA
0.18692
40 / 214
Toscani
0.17172
34 / 198
Esan, Nigeria
0.37981
79 / 208
Japanese
0.25980
53 / 204
Indian Telugu
0.19412
33 / 170
Peruvian
0.13131
26 / 198
Utah Europeans
0.22124
50 / 226
Gambian
0.44444
88 / 198
Kinh, Vietnam
0.24479
47 / 192
Punjabi, Lahore
0.20673
43 / 208
Puerto Rican
0.19697
39 / 198
Luhya, Kenya
0.46190
97 / 210
Southern Han
0.25980
53 / 204
Tamil
0.20588
35 / 170
Mende
0.19907
43 / 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 conservative benign benign
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) 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.