Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
c.103781G>A | p.R34594H (Arg > His) | substitution | missense | chr2:179397561 (reverse strand) | 0.17534783 |
As this variant is present at a population frequency of 0.17534783 (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 | 0.14551590 9703 / 66680 | 0.06744898 661 / 9800 | 0.43386120 3726 / 8588 | 0.25505877 4210 / 16506 | 0.14920194 1720 / 11528 | 0.14763780 975 / 6604 | 0.17000000 153 / 900 | 0.17534783 21148 / 120606 |
ESP | 0.14418 1201 / 8330 |
0.07377 293 / 3972 |
0.12144 1494 / 12302 |
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1KG |
0.13243 107 / 808 |
0.06657 88 / 1322 |
0.44841 452 / 1008 |
0.26789 262 / 978 |
0.14841 103 / 694 |
0.16667 33 / 198 |
0.20867 1045 / 5008 |
0.13736 25 / 182 British |
0.06557 8 / 122 African-American |
0.58065 108 / 186 Chinese Dai |
0.29651 51 / 172 Bengali |
0.14362 27 / 188 Colombian |
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0.14953 32 / 214 Iberian |
0.08333 16 / 192 African-Caribbean |
0.35437 73 / 206 Han, Beijing |
0.25243 52 / 206 Gujarati Indian |
0.09375 12 / 128 Mexican, LA |
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0.12150 26 / 214 Toscani |
0.06061 12 / 198 Esan, Nigeria |
0.43269 90 / 208 Japanese |
0.27451 56 / 204 Indian Telugu |
0.17647 30 / 170 Peruvian |
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0.12121 24 / 198 Utah Europeans |
0.06195 14 / 226 Gambian |
0.44949 89 / 198 Kinh, Vietnam |
0.26042 50 / 192 Punjabi, Lahore |
0.16346 34 / 208 Puerto Rican |
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0.03030 6 / 198 Luhya, Kenya |
0.43810 92 / 210 Southern Han |
0.25980 53 / 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 37.5% of algorithms have predicted that this variant will adversely affect protein function |
damaging | conservative | probably damaging | probably damaging | |
LRT | MutationTaster | MutationAssessor | FATHMM | |
polymorphism (auto) | neutral | 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.