TTN : c.11422C>T

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.11422C>Tp.P3808S (Pro > Ser)substitutionmissense chr2:179606538 (reverse strand)0.18877877

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.18877877 (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
ExAC0.08539871
5072 / 59392		0.43710157
4114 / 9412		0.25390219
1952 / 7688		0.22518442
3480 / 15454		0.48858491
5179 / 10600		0.12137331
753 / 6204		0.16425121
136 / 828		0.18877877
20686 / 109578
ESP 0.07316
597 / 8160		 0.42081
1541 / 3662		 0.18085
2138 / 11822
1KG
 0.07921
64 / 808		 0.45310
599 / 1322		 0.21329
215 / 1008		 0.22086
216 / 978		 0.36023
250 / 694		 0.12121
24 / 198		 0.27316
1368 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.07692
14 / 182
British
0.44262
54 / 122
African-American
0.18817
35 / 186
Chinese Dai
0.26163
45 / 172
Bengali
0.28191
53 / 188
Colombian
0.07944
17 / 214
Iberian
0.45833
88 / 192
African-Caribbean
0.23301
48 / 206
Han, Beijing
0.17961
37 / 206
Gujarati Indian
0.39062
50 / 128
Mexican, LA
0.05607
12 / 214
Toscani
0.52020
103 / 198
Esan, Nigeria
0.21635
45 / 208
Japanese
0.22059
45 / 204
Indian Telugu
0.64706
110 / 170
Peruvian
0.10606
21 / 198
Utah Europeans
0.47788
108 / 226
Gambian
0.18687
37 / 198
Kinh, Vietnam
0.21875
42 / 192
Punjabi, Lahore
0.17788
37 / 208
Puerto Rican
0.39899
79 / 198
Luhya, Kenya
0.23810
50 / 210
Southern Han
0.23039
47 / 204
Tamil
0.43529
74 / 170
Mende
0.43056
93 / 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.