TTN : c.74839C>T

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.74839C>Tp.R24947C (Arg > Cys)substitutionmissense chr2:179436020 (reverse strand)0.17455999

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.17455999 (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
ExAC0.14477236
9654 / 66684		0.06749030
661 / 9794		0.43245779
3688 / 8528		0.25411921
4195 / 16508		0.14893433
1719 / 11542		0.14765507
976 / 6610		0.17000000
153 / 900		0.17455999
21046 / 120566
ESP 0.14422
1195 / 8286		 0.07457
288 / 3862		 0.12208
1483 / 12148
1KG
 0.12995
105 / 808		 0.06657
88 / 1322		 0.45040
454 / 1008		 0.26687
261 / 978		 0.14553
101 / 694		 0.16667
33 / 198		 0.20807
1042 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.13736
25 / 182
British
0.06557
8 / 122
African-American
0.58065
108 / 186
Chinese Dai
0.29651
51 / 172
Bengali
0.14362
27 / 188
Colombian
0.14019
30 / 214
Iberian
0.08333
16 / 192
African-Caribbean
0.36408
75 / 206
Han, Beijing
0.25243
52 / 206
Gujarati Indian
0.08594
11 / 128
Mexican, LA
0.12150
26 / 214
Toscani
0.06061
12 / 198
Esan, Nigeria
0.43269
90 / 208
Japanese
0.27451
56 / 204
Indian Telugu
0.17059
29 / 170
Peruvian
0.12121
24 / 198
Utah Europeans
0.06195
14 / 226
Gambian
0.44444
88 / 198
Kinh, Vietnam
0.25521
49 / 192
Punjabi, Lahore
0.16346
34 / 208
Puerto Rican
0.03030
6 / 198
Luhya, Kenya
0.44286
93 / 210
Southern Han
0.25980
53 / 204
Tamil
0.07059
12 / 170
Mende
0.09259
20 / 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
62.5% of algorithms have predicted that this variant will adversely affect protein function
damaging radical probably damaging possibly damaging
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) medium 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.