Variant (CDS) | Variant (protein) | Variant Type | Variant Effect | Genomic Location (GRCh37) | ExAC Frequency |
c.19301G>A | p.S6434N (Ser > Asn) | substitution | missense | chr2:179593352 (reverse strand) | 0.06986004 |
As this variant is present at a population frequency of 0.06986004 (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 | 0.02748103 1811 / 65900 | 0.08693852 840 / 9662 | 0.02558915 215 / 8402 | 0.17503359 2866 / 16374 | 0.18910768 2132 / 11274 | 0.05798654 379 / 6536 | 0.08202247 73 / 890 | 0.06986004 8316 / 119038 |
ESP | 0.02462 202 / 8206 |
0.08338 307 / 3682 |
0.04282 509 / 11888 |
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1KG |
0.02723 22 / 808 |
0.08699 115 / 1322 |
0.02381 24 / 1008 |
0.19121 187 / 978 |
0.15130 105 / 694 |
0.07071 14 / 198 |
0.09325 467 / 5008 |
0.03297 6 / 182 British |
0.12295 15 / 122 African-American |
0.04301 8 / 186 Chinese Dai |
0.20930 36 / 172 Bengali |
0.14894 28 / 188 Colombian |
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0.02336 5 / 214 Iberian |
0.10417 20 / 192 African-Caribbean |
0.01456 3 / 206 Han, Beijing |
0.18447 38 / 206 Gujarati Indian |
0.17188 22 / 128 Mexican, LA |
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0.02336 5 / 214 Toscani |
0.08081 16 / 198 Esan, Nigeria |
0.00000 0 / 208 Japanese |
0.19608 40 / 204 Indian Telugu |
0.25294 43 / 170 Peruvian |
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0.03030 6 / 198 Utah Europeans |
0.11504 26 / 226 Gambian |
0.05556 11 / 198 Kinh, Vietnam |
0.14583 28 / 192 Punjabi, Lahore |
0.05769 12 / 208 Puerto Rican |
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0.05051 10 / 198 Luhya, Kenya |
0.00952 2 / 210 Southern Han |
0.22059 45 / 204 Tamil |
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0.08824 15 / 170 Mende |
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0.06019 13 / 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 50% of algorithms have predicted that this variant will adversely affect protein function |
damaging | conservative | possibly damaging | possibly damaging | |
LRT | MutationTaster | MutationAssessor | FATHMM | |
polymorphism (auto) | 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.