TTN : c.100096G>A

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.100096G>Ap.V33366I (Val > Ile)substitutionmissense chr2:179401740 (reverse strand)0.02881643

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.02881643 (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
ExAC0.02658442
1698 / 63872
0.00389948
36 / 9232
0.07139376
586 / 8208
0.00773365
118 / 15258
0.03747902
402 / 10726
0.06838143
436 / 6376
0.02836879
24 / 846
0.02881643
3300 / 114518
ESP 0.02071
171 / 8258
0.00522
20 / 3834
0.01580
191 / 12092
1KG
0.02104
17 / 808
0.00076
1 / 1322
0.06250
63 / 1008
0.00716
7 / 978
0.02450
17 / 694
0.05556
11 / 198
0.02316
116 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.01648
3 / 182
British
0.00000
0 / 122
African-American
0.05376
10 / 186
Chinese Dai
0.02907
5 / 172
Bengali
0.00000
0 / 188
Colombian
0.01869
4 / 214
Iberian
0.00521
1 / 192
African-Caribbean
0.07767
16 / 206
Han, Beijing
0.00485
1 / 206
Gujarati Indian
0.02344
3 / 128
Mexican, LA
0.01402
3 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.04808
10 / 208
Japanese
0.00000
0 / 204
Indian Telugu
0.06471
11 / 170
Peruvian
0.03535
7 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.05051
10 / 198
Kinh, Vietnam
0.00521
1 / 192
Punjabi, Lahore
0.01442
3 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.08095
17 / 210
Southern Han
0.00000
0 / 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
50% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative probably damaging probably damaging
LRT MutationTaster MutationAssessor FATHMM
disease-causing 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.