TTN : c.98912G>A

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.98912G>Ap.R32971H (Arg > His)substitutionmissense chr2:179403750 (reverse strand)0.06803364

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.06803364 (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
ExAC0.03236892
2157 / 66638
0.01346115
132 / 9806
0.02571562
221 / 8594
0.18126742
2992 / 16506
0.19527450
2248 / 11512
0.05907301
390 / 6602
0.06888889
62 / 900
0.06803364
8202 / 120558
ESP 0.02872
243 / 8460
0.01582
67 / 4236
0.02442
310 / 12696
1KG
0.03960
32 / 808
0.01135
15 / 1322
0.02480
25 / 1008
0.19836
194 / 978
0.14841
103 / 694
0.08081
16 / 198
0.07688
385 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.04396
8 / 182
British
0.02459
3 / 122
African-American
0.04839
9 / 186
Chinese Dai
0.20349
35 / 172
Bengali
0.14894
28 / 188
Colombian
0.03271
7 / 214
Iberian
0.02083
4 / 192
African-Caribbean
0.01456
3 / 206
Han, Beijing
0.19903
41 / 206
Gujarati Indian
0.17188
22 / 128
Mexican, LA
0.04673
10 / 214
Toscani
0.01515
3 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.21569
44 / 204
Indian Telugu
0.23529
40 / 170
Peruvian
0.03535
7 / 198
Utah Europeans
0.01770
4 / 226
Gambian
0.05051
10 / 198
Kinh, Vietnam
0.15625
30 / 192
Punjabi, Lahore
0.06250
13 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.01429
3 / 210
Southern Han
0.21569
44 / 204
Tamil
0.00000
0 / 170
Mende
0.00463
1 / 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
62.5% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative probably damaging probably damaging
LRT MutationTaster MutationAssessor FATHMM
disease-causing high 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.