TNNI3 : c.143A>C
Variant Details
| Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
| c.143A>C | p.Q48P (Gln > Pro) | substitution | missense | chr19:55667978 (reverse strand) | 0.00012526 |
Effect in Cardiac Disease
As this variant is present at a population frequency of 0.00012526 (ExAC mean allelic frequency), it is unlikely to be pathogenic.
| HCM | OMGL: Detected in 0 / 3135 HCM patients. LMM: Detected in 0 / 2912 HCM patients. |
|---|---|
| DCM | OMGL: Detected in 0 / 483 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 |
|---|---|---|---|---|---|---|---|---|
| ExAC | 0.00000000 0 / 10952 | 0.00000000 0 / 2682 | 0.00000000 0 / 1100 | 0.00036711 3 / 8172 | 0.00000000 0 / 666 | 0.00000000 0 / 150 | 0.00000000 0 / 228 | 0.00012526 3 / 23950 |
| ESP | 0.00000 0 / 8600 |
0.00000 0 / 4400 |
0.00000 0 / 13000 |
|||||
| 1KG |
0.00000 0 / 1006 |
0.00000 0 / 1322 |
0.00000 0 / 1008 |
0.00000 0 / 978 |
0.00000 0 / 694 |
0.00000 0 / 198 |
0.00000 0 / 5008 |
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 | ENST00000344887 | LRG_432t1 | NM_000363.4 | |
| Protein | ENSP00000341838 | LRG_432p1 | P19429 |
| Missense Variant Predictions | ||||
|---|---|---|---|---|
| SIFT | Grantham | Polyphen-DIV | Polyphen-VAR | Summary 62.5% of algorithms have predicted that this variant will adversely affect protein function   |
| tolerated | moderately conservative | possibly damaging | possibly damaging | |
| LRT | MutationTaster | MutationAssessor | FATHMM | |
| deleterious | disease-causing | 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.