TTN : c.42958A>G

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.42958A>Gp.K14320E (Lys > Glu)substitutionmissense chr2:179498042 (reverse strand)0.08302503

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.08302503 (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
ExAC0.10425794
6949 / 66652		0.01724490
169 / 9800		0.00702741
60 / 8538		0.10027872
1655 / 16504		0.04067151
470 / 11556		0.09551922
631 / 6606		0.08351893
75 / 898		0.08302503
10009 / 120554
ESP 0.10978
898 / 8180		 0.01796
66 / 3674		 0.08132
964 / 11854
1KG
 0.09777
79 / 808		 0.00605
8 / 1322		 0.00496
5 / 1008		 0.10020
98 / 978		 0.06196
43 / 694		 0.11111
22 / 198		 0.05092
255 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.09341
17 / 182
British
0.03279
4 / 122
African-American
0.00000
0 / 186
Chinese Dai
0.05814
10 / 172
Bengali
0.05851
11 / 188
Colombian
0.07477
16 / 214
Iberian
0.01042
2 / 192
African-Caribbean
0.00971
2 / 206
Han, Beijing
0.12136
25 / 206
Gujarati Indian
0.06250
8 / 128
Mexican, LA
0.11682
25 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.09804
20 / 204
Indian Telugu
0.03529
6 / 170
Peruvian
0.10606
21 / 198
Utah Europeans
0.00442
1 / 226
Gambian
0.01010
2 / 198
Kinh, Vietnam
0.09375
18 / 192
Punjabi, Lahore
0.08654
18 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.00476
1 / 210
Southern Han
0.12255
25 / 204
Tamil
0.00588
1 / 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
37.5% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative probably damaging probably damaging
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.