TTN : c.25064C>A

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.25064C>Ap.A8355E (Ala > Glu)substitutionmissense chr2:179582537 (reverse strand)0.30876983

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.30876983 (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
ExAC0.20370827
13228 / 64936
0.42477316
4026 / 9478
0.66579136
5578 / 8378
0.44837513
7009 / 15632
0.41845910
4747 / 11344
0.20590923
1352 / 6566
0.28668172
254 / 886
0.30876983
36194 / 117220
ESP 0.20183
1653 / 8190
0.40752
1507 / 3698
0.26581
3160 / 11888
1KG
0.22649
183 / 808
0.46369
613 / 1322
0.65774
663 / 1008
0.47342
463 / 978
0.37896
263 / 694
0.21717
43 / 198
0.44489
2228 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.26374
48 / 182
British
0.45902
56 / 122
African-American
0.69892
130 / 186
Chinese Dai
0.52326
90 / 172
Bengali
0.35638
67 / 188
Colombian
0.21495
46 / 214
Iberian
0.42708
82 / 192
African-Caribbean
0.62621
129 / 206
Han, Beijing
0.41262
85 / 206
Gujarati Indian
0.37500
48 / 128
Mexican, LA
0.23364
50 / 214
Toscani
0.47980
95 / 198
Esan, Nigeria
0.59615
124 / 208
Japanese
0.48529
99 / 204
Indian Telugu
0.50588
86 / 170
Peruvian
0.19697
39 / 198
Utah Europeans
0.53540
121 / 226
Gambian
0.67172
133 / 198
Kinh, Vietnam
0.45833
88 / 192
Punjabi, Lahore
0.29808
62 / 208
Puerto Rican
0.41414
82 / 198
Luhya, Kenya
0.70000
147 / 210
Southern Han
0.49510
101 / 204
Tamil
0.50588
86 / 170
Mende
0.42130
91 / 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
25% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately radical
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.