TTN : c.28313G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.28313G>Ap.R9438Q (Arg > Gln)substitutionmissense chr2:179575511 (reverse strand)0.04511639

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.04511639 (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
ExAC0.05179390
3456 / 66726		0.01020616
100 / 9798		0.00000000
0 / 8618		0.03476260
574 / 16512		0.09928955
1146 / 11542		0.02041125
135 / 6614		0.03888889
35 / 900		0.04511639
5446 / 120710
ESP 0.05702
476 / 8348		 0.01411
56 / 3968		 0.04320
532 / 12316
1KG
 0.06064
49 / 808		 0.00000
0 / 1322		 0.00000
0 / 1008		 0.02658
26 / 978		 0.08069
56 / 694		 0.03030
6 / 198		 0.02736
137 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.07692
14 / 182
British
0.00000
0 / 122
African-American
0.00000
0 / 186
Chinese Dai
0.02326
4 / 172
Bengali
0.08511
16 / 188
Colombian
0.04206
9 / 214
Iberian
0.00000
0 / 192
African-Caribbean
0.00000
0 / 206
Han, Beijing
0.02427
5 / 206
Gujarati Indian
0.05469
7 / 128
Mexican, LA
0.05140
11 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.01471
3 / 204
Indian Telugu
0.15294
26 / 170
Peruvian
0.07576
15 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.00000
0 / 198
Kinh, Vietnam
0.04688
9 / 192
Punjabi, Lahore
0.03365
7 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.00000
0 / 210
Southern Han
0.02451
5 / 204
Tamil
0.00000
0 / 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
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.