TTN : c.982C>T

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.982C>Tp.R328C (Arg > Cys)substitutionmissense chr2:179659912 (reverse strand)0.12379053

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.12379053 (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
ExAC0.05083933
3392 / 66720		0.16548077
1721 / 10400		0.59677045
5137 / 8608		0.19176257
3166 / 16510		0.10402627
1204 / 11574		0.04898700
324 / 6614		0.08370044
76 / 908		0.12379053
15020 / 121334
ESP 0.05314
457 / 8600		 0.15638
689 / 4406		 0.08811
1146 / 13006
1KG
 0.05074
41 / 808		 0.19743
261 / 1322		 0.58829
593 / 1008		 0.21677
212 / 978		 0.09798
68 / 694		 0.03535
7 / 198		 0.23602
1182 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.06593
12 / 182
British
0.18033
22 / 122
African-American
0.60215
112 / 186
Chinese Dai
0.25581
44 / 172
Bengali
0.11170
21 / 188
Colombian
0.04206
9 / 214
Iberian
0.15625
30 / 192
African-Caribbean
0.57767
119 / 206
Han, Beijing
0.15534
32 / 206
Gujarati Indian
0.07031
9 / 128
Mexican, LA
0.05607
12 / 214
Toscani
0.18687
37 / 198
Esan, Nigeria
0.55769
116 / 208
Japanese
0.25000
51 / 204
Indian Telugu
0.10588
18 / 170
Peruvian
0.04040
8 / 198
Utah Europeans
0.20354
46 / 226
Gambian
0.58081
115 / 198
Kinh, Vietnam
0.19792
38 / 192
Punjabi, Lahore
0.09615
20 / 208
Puerto Rican
0.19192
38 / 198
Luhya, Kenya
0.62381
131 / 210
Southern Han
0.23039
47 / 204
Tamil
0.25294
43 / 170
Mende
0.20833
45 / 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 radical 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.