TTN : c.67075G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.67075G>Ap.V22359I (Val > Ile)substitutionmissense chr2:179444939 (reverse strand)0.24199386

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.24199386 (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
ExAC0.17757587
11785 / 66366		0.33156065
3242 / 9778		0.60167665
5024 / 8350		0.33121135
5463 / 16494		0.19267016
2208 / 11460		0.16554980
1087 / 6566		0.23266219
208 / 894		0.24199386
29017 / 119908
ESP 0.17691
1445 / 8168		 0.32853
1207 / 3674		 0.22395
2652 / 11842
1KG
 0.18564
150 / 808		 0.34342
454 / 1322		 0.63095
636 / 1008		 0.34151
334 / 978		 0.21470
149 / 694		 0.18182
36 / 198		 0.35124
1759 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.18132
33 / 182
British
0.29508
36 / 122
African-American
0.73118
136 / 186
Chinese Dai
0.41279
71 / 172
Bengali
0.23404
44 / 188
Colombian
0.19626
42 / 214
Iberian
0.28646
55 / 192
African-Caribbean
0.57767
119 / 206
Han, Beijing
0.30097
62 / 206
Gujarati Indian
0.14844
19 / 128
Mexican, LA
0.22430
48 / 214
Toscani
0.40909
81 / 198
Esan, Nigeria
0.58654
122 / 208
Japanese
0.32843
67 / 204
Indian Telugu
0.20000
34 / 170
Peruvian
0.13636
27 / 198
Utah Europeans
0.37611
85 / 226
Gambian
0.63636
126 / 198
Kinh, Vietnam
0.35417
68 / 192
Punjabi, Lahore
0.25000
52 / 208
Puerto Rican
0.29798
59 / 198
Luhya, Kenya
0.63333
133 / 210
Southern Han
0.32353
66 / 204
Tamil
0.35882
61 / 170
Mende
0.35648
77 / 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
12.5% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative benign 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.