Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
c.14525G>A | p.R4842K (Arg > Lys) | substitution | missense | chr2:179600648 (reverse strand) | 0.09585600 |
As this variant is present at a population frequency of 0.09585600 (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 | 0.04998950 3333 / 66674 | 0.21587431 2116 / 9802 | 0.21328671 1830 / 8580 | 0.04330709 715 / 16510 | 0.27071775 3123 / 11536 | 0.05750605 380 / 6608 | 0.07126949 64 / 898 | 0.09585600 11561 / 120608 |
ESP | 0.04789 397 / 8290 |
0.20325 789 / 3882 |
0.09744 1186 / 12172 |
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1KG |
0.05074 41 / 808 |
0.22844 302 / 1322 |
0.19345 195 / 1008 |
0.04397 43 / 978 |
0.19164 133 / 694 |
0.05556 11 / 198 |
0.14477 725 / 5008 |
0.04396 8 / 182 British |
0.20492 25 / 122 African-American |
0.14516 27 / 186 Chinese Dai |
0.05233 9 / 172 Bengali |
0.11702 22 / 188 Colombian |
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0.05140 11 / 214 Iberian |
0.19792 38 / 192 African-Caribbean |
0.21845 45 / 206 Han, Beijing |
0.01456 3 / 206 Gujarati Indian |
0.21094 27 / 128 Mexican, LA |
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0.03271 7 / 214 Toscani |
0.25758 51 / 198 Esan, Nigeria |
0.21635 45 / 208 Japanese |
0.03922 8 / 204 Indian Telugu |
0.38235 65 / 170 Peruvian |
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0.07576 15 / 198 Utah Europeans |
0.23451 53 / 226 Gambian |
0.15152 30 / 198 Kinh, Vietnam |
0.08854 17 / 192 Punjabi, Lahore |
0.09135 19 / 208 Puerto Rican |
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0.24242 48 / 198 Luhya, Kenya |
0.22857 48 / 210 Southern Han |
0.02941 6 / 204 Tamil |
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0.25882 44 / 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 | |||
LRT | MutationTaster | MutationAssessor | FATHMM | |
polymorphism (auto) | 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.