TTN : c.100579G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.100579G>Ap.V33527I (Val > Ile)substitutionmissense chr2:179400895 (reverse strand)0.03121425

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.03121425 (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
ExAC0.01820562
1196 / 65694		0.07135449
688 / 9642		0.14669031
1241 / 8460		0.01381925
226 / 16354		0.02799929
316 / 11286		0.00213350
14 / 6562		0.03370787
30 / 890		0.03121425
3711 / 118888
ESP 0.01738
143 / 8230		 0.06507
247 / 3796		 0.03243
390 / 12026
1KG
 0.03589
29 / 808		 0.08472
112 / 1322		 0.14881
150 / 1008		 0.01125
11 / 978		 0.03602
25 / 694		 0.00505
1 / 198		 0.06550
328 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.03297
6 / 182
British
0.08197
10 / 122
African-American
0.12366
23 / 186
Chinese Dai
0.02326
4 / 172
Bengali
0.03723
7 / 188
Colombian
0.03738
8 / 214
Iberian
0.06250
12 / 192
African-Caribbean
0.15049
31 / 206
Han, Beijing
0.00000
0 / 206
Gujarati Indian
0.03906
5 / 128
Mexican, LA
0.06075
13 / 214
Toscani
0.07576
15 / 198
Esan, Nigeria
0.14423
30 / 208
Japanese
0.00490
1 / 204
Indian Telugu
0.02353
4 / 170
Peruvian
0.01010
2 / 198
Utah Europeans
0.12832
29 / 226
Gambian
0.16667
33 / 198
Kinh, Vietnam
0.02083
4 / 192
Punjabi, Lahore
0.04327
9 / 208
Puerto Rican
0.08081
16 / 198
Luhya, Kenya
0.15714
33 / 210
Southern Han
0.00980
2 / 204
Tamil
0.10000
17 / 170
Mende
0.06019
13 / 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
25% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative possibly damaging 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.