TNNT2 : c.758A>G

TNNT2 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.758A>Gp.K253R (Lys > Arg)substitutionmissense chr1:201330429 (reverse strand)0.05073395

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.05073395 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

HCM

OMGL: Detected in 0 / 3191 HCM patients.

LMM:   Detected in 0 / 2912 HCM patients.

DCM

OMGL: Detected in 0 / 498 DCM patients.

LMM:   Detected in 0 / 756 DCM patients.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases



Database European African East Asian South Asian American Finnish Other Total
ExAC0.01621217
1082 / 66740		0.15270037
1589 / 10406		0.04756944
411 / 8640		0.14637839
2417 / 16512		0.02323372
269 / 11578		0.05170850
342 / 6614		0.05396476
49 / 908		0.05073395
6159 / 121398
ESP 0.01477
127 / 8600		 0.14889
656 / 4406		 0.06020
783 / 13006
1KG
 0.01733
14 / 808		 0.17398
230 / 1322		 0.04663
47 / 1008		 0.17689
173 / 978		 0.02305
16 / 694		 0.04040
8 / 198		 0.09744
488 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.01648
3 / 182
British
0.12295
15 / 122
African-American
0.04839
9 / 186
Chinese Dai
0.20930
36 / 172
Bengali
0.01064
2 / 188
Colombian
0.02336
5 / 214
Iberian
0.19792
38 / 192
African-Caribbean
0.03883
8 / 206
Han, Beijing
0.17476
36 / 206
Gujarati Indian
0.01562
2 / 128
Mexican, LA
0.02336
5 / 214
Toscani
0.18182
36 / 198
Esan, Nigeria
0.07212
15 / 208
Japanese
0.16667
34 / 204
Indian Telugu
0.02353
4 / 170
Peruvian
0.00505
1 / 198
Utah Europeans
0.20354
46 / 226
Gambian
0.03030
6 / 198
Kinh, Vietnam
0.16146
31 / 192
Punjabi, Lahore
0.03846
8 / 208
Puerto Rican
0.13636
27 / 198
Luhya, Kenya
0.04286
9 / 210
Southern Han
0.17647
36 / 204
Tamil
0.15294
26 / 170
Mende
0.19444
42 / 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 ENST00000367318 LRG_431t2NM_001001430.1
Protein ENSP00000356287 LRG_431p2

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
12.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated conservative benign benign
LRT MutationTaster MutationAssessor FATHMM
neutral polymorphism (auto) low impact damaging


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.