TTN : c.4715G>A

TTN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.4715G>Ap.R1572Q (Arg > Gln)substitutionmissense chr2:179641975 (reverse strand)0.07111511

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.07111511 (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
ExAC0.04556635
3038 / 66672		0.01047674
109 / 10404		0.20633442
1772 / 8588		0.01835919
303 / 16504		0.25784365
2975 / 11538		0.05732002
379 / 6612		0.04955947
45 / 908		0.07111511
8621 / 121226
ESP 0.04302
370 / 8600		 0.01339
59 / 4406		 0.03298
429 / 13006
1KG
 0.04703
38 / 808		 0.00227
3 / 1322		 0.18948
191 / 1008		 0.01534
15 / 978		 0.17147
119 / 694		 0.05556
11 / 198		 0.07528
377 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.04396
8 / 182
British
0.01639
2 / 122
African-American
0.14516
27 / 186
Chinese Dai
0.02326
4 / 172
Bengali
0.09043
17 / 188
Colombian
0.04206
9 / 214
Iberian
0.00521
1 / 192
African-Caribbean
0.19903
41 / 206
Han, Beijing
0.00971
2 / 206
Gujarati Indian
0.17188
22 / 128
Mexican, LA
0.02336
5 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.23077
48 / 208
Japanese
0.00980
2 / 204
Indian Telugu
0.38235
65 / 170
Peruvian
0.08081
16 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.14646
29 / 198
Kinh, Vietnam
0.02604
5 / 192
Punjabi, Lahore
0.07212
15 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.21905
46 / 210
Southern Han
0.00980
2 / 204
Tamil
0.00000
0 / 170
Mende
0.00000
0 / 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 conservative possibly damaging 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.