Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
c.25274G>A | p.S8425N (Ser > Asn) | substitution | missense | chr2:179582327 (reverse strand) | 0.17836272 |
As this variant is present at a population frequency of 0.17836272 (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 | 0.14611404 9543 / 65312 | 0.16611157 1596 / 9608 | 0.42644231 3548 / 8320 | 0.22572696 3664 / 16232 | 0.17562980 1966 / 11194 | 0.09285933 606 / 6526 | 0.15532880 137 / 882 | 0.17836272 21060 / 118074 |
ESP | 0.15077 1242 / 8238 |
0.16295 613 / 3762 |
0.15458 1855 / 12000 |
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1KG |
0.17327 140 / 808 |
0.19365 256 / 1322 |
0.43552 439 / 1008 |
0.24642 241 / 978 |
0.18300 127 / 694 |
0.09091 18 / 198 |
0.24381 1221 / 5008 |
0.20879 38 / 182 British |
0.18033 22 / 122 African-American |
0.50538 94 / 186 Chinese Dai |
0.25000 43 / 172 Bengali |
0.18085 34 / 188 Colombian |
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0.16822 36 / 214 Iberian |
0.17188 33 / 192 African-Caribbean |
0.39320 81 / 206 Han, Beijing |
0.21845 45 / 206 Gujarati Indian |
0.13281 17 / 128 Mexican, LA |
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0.18692 40 / 214 Toscani |
0.17172 34 / 198 Esan, Nigeria |
0.37981 79 / 208 Japanese |
0.25980 53 / 204 Indian Telugu |
0.19412 33 / 170 Peruvian |
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0.13131 26 / 198 Utah Europeans |
0.22124 50 / 226 Gambian |
0.44444 88 / 198 Kinh, Vietnam |
0.24479 47 / 192 Punjabi, Lahore |
0.20673 43 / 208 Puerto Rican |
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0.19697 39 / 198 Luhya, Kenya |
0.46190 97 / 210 Southern Han |
0.25980 53 / 204 Tamil |
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0.20588 35 / 170 Mende |
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0.19907 43 / 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 | 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.