TTN : c.9461A>G

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.9461A>Gp.K3154R (Lys > Arg)substitutionmissense chr2:179632496 (reverse strand)0.06588968

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.06588968 (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
ExAC0.02427345
1617 / 66616		0.07307618
754 / 10318		0.02416530
207 / 8566		0.16806061
2773 / 16500		0.18871191
2180 / 11552		0.05722071
378 / 6606		0.07488987
68 / 908		0.06588968
7977 / 121066
ESP 0.02116
182 / 8600		 0.07195
317 / 4406		 0.03837
499 / 13006
1KG
 0.02599
21 / 808		 0.07489
99 / 1322		 0.02083
21 / 1008		 0.17280
169 / 978		 0.15418
107 / 694		 0.07071
14 / 198		 0.08606
431 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.02747
5 / 182
British
0.12295
15 / 122
African-American
0.04301
8 / 186
Chinese Dai
0.19767
34 / 172
Bengali
0.14894
28 / 188
Colombian
0.02804
6 / 214
Iberian
0.07812
15 / 192
African-Caribbean
0.01942
4 / 206
Han, Beijing
0.16019
33 / 206
Gujarati Indian
0.17969
23 / 128
Mexican, LA
0.02336
5 / 214
Toscani
0.07071
14 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.18137
37 / 204
Indian Telugu
0.25882
44 / 170
Peruvian
0.02525
5 / 198
Utah Europeans
0.10177
23 / 226
Gambian
0.03535
7 / 198
Kinh, Vietnam
0.13021
25 / 192
Punjabi, Lahore
0.05769
12 / 208
Puerto Rican
0.04040
8 / 198
Luhya, Kenya
0.00952
2 / 210
Southern Han
0.19608
40 / 204
Tamil
0.07059
12 / 170
Mende
0.05556
12 / 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.