Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
c.53123A>T | p.K17708I (Lys > Ile) | substitution | missense | chr2:179472292 (reverse strand) | 0.02915851 |
As this variant is present at a population frequency of 0.02915851 (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.
Database | European | African | East Asian | South Asian | American | Finnish | Other | Total |
---|---|---|---|---|---|---|---|---|
ExAC | 0.02544205 1695 / 66622 | 0.00369382 36 / 9746 | 0.10320781 888 / 8604 | 0.00696970 115 / 16500 | 0.03528801 408 / 11562 | 0.05276686 349 / 6614 | 0.02666667 24 / 900 | 0.02915851 3515 / 120548 |
ESP | 0.02040 168 / 8236 |
0.00531 20 / 3770 |
0.01566 188 / 12006 |
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1KG |
0.01733 14 / 808 |
0.00076 1 / 1322 |
0.09921 100 / 1008 |
0.00613 6 / 978 |
0.02450 17 / 694 |
0.05051 10 / 198 |
0.02955 148 / 5008 |
0.01099 2 / 182 British |
0.00000 0 / 122 African-American |
0.10215 19 / 186 Chinese Dai |
0.02326 4 / 172 Bengali |
0.00532 1 / 188 Colombian |
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0.00935 2 / 214 Iberian |
0.00521 1 / 192 African-Caribbean |
0.08738 18 / 206 Han, Beijing |
0.00485 1 / 206 Gujarati Indian |
0.01562 2 / 128 Mexican, LA |
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0.01402 3 / 214 Toscani |
0.00000 0 / 198 Esan, Nigeria |
0.09135 19 / 208 Japanese |
0.00000 0 / 204 Indian Telugu |
0.06471 11 / 170 Peruvian |
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0.03535 7 / 198 Utah Europeans |
0.00000 0 / 226 Gambian |
0.09091 18 / 198 Kinh, Vietnam |
0.00521 1 / 192 Punjabi, Lahore |
0.01442 3 / 208 Puerto Rican |
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0.00000 0 / 198 Luhya, Kenya |
0.12381 26 / 210 Southern Han |
0.00000 0 / 204 Tamil |
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0.00000 0 / 170 Mende |
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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).
Canonical Sequences | ||||
---|---|---|---|---|
Transcript | ENST00000589042 | LRG_391t1 | NM_001267550.1 | |
Protein | ENSP00000467141 | LRG_391p1 |
Missense Variant Predictions | ||||
---|---|---|---|---|
SIFT | Grantham | Polyphen-DIV | Polyphen-VAR | Summary 37.5% of algorithms have predicted that this variant will adversely affect protein function |
damaging | moderately radical | benign | benign | |
LRT | MutationTaster | MutationAssessor | FATHMM | |
polymorphism | medium impact | tolerated |
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.