Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
c.59585C>T | p.P19862L (Pro > Leu) | substitution | missense | chr2:179457147 (reverse strand) | 0.17678385 |
As this variant is present at a population frequency of 0.17678385 (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 | 0.14614577 9745 / 66680 | 0.06781046 664 / 9792 | 0.43535188 3724 / 8554 | 0.25990789 4289 / 16502 | 0.15263797 1759 / 11524 | 0.14794064 977 / 6604 | 0.17149220 154 / 898 | 0.17678385 21312 / 120554 |
ESP | 0.14735 1205 / 8178 |
0.07653 283 / 3698 |
0.12529 1488 / 11876 |
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1KG |
0.13243 107 / 808 |
0.06657 88 / 1322 |
0.45734 461 / 1008 |
0.27812 272 / 978 |
0.15274 106 / 694 |
0.16667 33 / 198 |
0.21306 1067 / 5008 |
0.13736 25 / 182 British |
0.06557 8 / 122 African-American |
0.59140 110 / 186 Chinese Dai |
0.30814 53 / 172 Bengali |
0.14894 28 / 188 Colombian |
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0.14486 31 / 214 Iberian |
0.08333 16 / 192 African-Caribbean |
0.36408 75 / 206 Han, Beijing |
0.27184 56 / 206 Gujarati Indian |
0.10156 13 / 128 Mexican, LA |
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0.12617 27 / 214 Toscani |
0.06061 12 / 198 Esan, Nigeria |
0.43269 90 / 208 Japanese |
0.28431 58 / 204 Indian Telugu |
0.17647 30 / 170 Peruvian |
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0.12121 24 / 198 Utah Europeans |
0.06195 14 / 226 Gambian |
0.45455 90 / 198 Kinh, Vietnam |
0.26562 51 / 192 Punjabi, Lahore |
0.16827 35 / 208 Puerto Rican |
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0.03030 6 / 198 Luhya, Kenya |
0.45714 96 / 210 Southern Han |
0.26471 54 / 204 Tamil |
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0.07059 12 / 170 Mende |
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0.09259 20 / 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 12.5% of algorithms have predicted that this variant will adversely affect protein function |
damaging | moderately conservative | benign | benign | |
LRT | MutationTaster | MutationAssessor | FATHMM | |
polymorphism (auto) | low 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.