TTN : c.58436G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.58436G>Ap.R19479H (Arg > His)substitutionmissense chr2:179458591 (reverse strand)0.17610566

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.17610566 (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
ExAC0.14649139
9628 / 65724		0.06803700
662 / 9730		0.43168317
3488 / 8080		0.26034964
4289 / 16474		0.15301268
1737 / 11352		0.14748092
966 / 6550		0.17004505
151 / 888		0.17610566
20921 / 118798
ESP 0.14728
1208 / 8202		 0.07651
284 / 3712		 0.12523
1492 / 11914
1KG
 0.13366
108 / 808		 0.06657
88 / 1322		 0.45437
458 / 1008		 0.27812
272 / 978		 0.15130
105 / 694		 0.16667
33 / 198		 0.21246
1064 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.13736
25 / 182
British
0.06557
8 / 122
African-American
0.58602
109 / 186
Chinese Dai
0.30814
53 / 172
Bengali
0.14362
27 / 188
Colombian
0.14486
31 / 214
Iberian
0.08333
16 / 192
African-Caribbean
0.35922
74 / 206
Han, Beijing
0.27184
56 / 206
Gujarati Indian
0.10156
13 / 128
Mexican, LA
0.12617
27 / 214
Toscani
0.06061
12 / 198
Esan, Nigeria
0.42788
89 / 208
Japanese
0.28431
58 / 204
Indian Telugu
0.17647
30 / 170
Peruvian
0.12626
25 / 198
Utah Europeans
0.06195
14 / 226
Gambian
0.45455
90 / 198
Kinh, Vietnam
0.26562
51 / 192
Punjabi, Lahore
0.16827
35 / 208
Puerto Rican
0.03030
6 / 198
Luhya, Kenya
0.45714
96 / 210
Southern Han
0.26471
54 / 204
Tamil
0.07059
12 / 170
Mende
0.09259
20 / 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
polymorphism (auto) medium 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.