TTN : c.67246G>C

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.67246G>Cp.A22416P (Ala > Pro)substitutionmissense chr2:179444768 (reverse strand)0.99862487

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.99862487 (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
ExAC0.99974527
66721 / 66738		0.98623573
9673 / 9808		1.00000000
8580 / 8580		1.00000000
16512 / 16512		0.99878935
11550 / 11564		1.00000000
6614 / 6614		1.00000000
900 / 900		0.99862487
120550 / 120716
ESP 0.99988
8261 / 8262		 0.98642
3778 / 3830		 0.99562
12039 / 12092
1KG
 1.00000
808 / 808		 0.98109
1297 / 1322		 1.00000
1008 / 1008		 1.00000
978 / 978		 0.99712
692 / 694		 1.00000
198 / 198		 0.99461
4981 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

1.00000
182 / 182
British
0.99180
121 / 122
African-American
1.00000
186 / 186
Chinese Dai
1.00000
172 / 172
Bengali
0.99468
187 / 188
Colombian
1.00000
214 / 214
Iberian
0.98438
189 / 192
African-Caribbean
1.00000
206 / 206
Han, Beijing
1.00000
206 / 206
Gujarati Indian
1.00000
128 / 128
Mexican, LA
1.00000
214 / 214
Toscani
0.97980
194 / 198
Esan, Nigeria
1.00000
208 / 208
Japanese
1.00000
204 / 204
Indian Telugu
1.00000
170 / 170
Peruvian
1.00000
198 / 198
Utah Europeans
0.97345
220 / 226
Gambian
1.00000
198 / 198
Kinh, Vietnam
1.00000
192 / 192
Punjabi, Lahore
0.99519
207 / 208
Puerto Rican
0.97475
193 / 198
Luhya, Kenya
1.00000
210 / 210
Southern Han
1.00000
204 / 204
Tamil
1.00000
170 / 170
Mende
0.97222
210 / 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) neutral 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.