Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19592 | 58999;59000;59001 | chr2:178593434;178593433;178593432 | chr2:179458161;179458160;179458159 |
| N2AB | 17951 | 54076;54077;54078 | chr2:178593434;178593433;178593432 | chr2:179458161;179458160;179458159 |
| N2A | 17024 | 51295;51296;51297 | chr2:178593434;178593433;178593432 | chr2:179458161;179458160;179458159 |
| N2B | 10527 | 31804;31805;31806 | chr2:178593434;178593433;178593432 | chr2:179458161;179458160;179458159 |
| Novex-1 | 10652 | 32179;32180;32181 | chr2:178593434;178593433;178593432 | chr2:179458161;179458160;179458159 |
| Novex-2 | 10719 | 32380;32381;32382 | chr2:178593434;178593433;178593432 | chr2:179458161;179458160;179458159 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs769094173  |
-0.651 | 0.906 | N | 0.375 | 0.243 | 0.32306181527 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/A | rs769094173 |
-0.651 | 0.906 | N | 0.375 | 0.243 | 0.32306181527 | gnomAD-4.0.0 | 1.02683E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.34944E-05 | 0 | 0 |
| T/I | rs745441183 |
-0.103 | 0.988 | N | 0.369 | 0.443 | 0.482209950775 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs745441183 |
-0.103 | 0.988 | N | 0.369 | 0.443 | 0.482209950775 | gnomAD-4.0.0 | 6.84572E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99648E-07 | 0 | 0 |
| T/N | rs745441183 |
None | 0.92 | N | 0.394 | 0.307 | 0.375861065471 | gnomAD-4.0.0 | 3.42286E-06 | None | None | None | None | N | None | 8.97451E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.31477E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1709 | likely_benign | 0.1623 | benign | -0.631 | Destabilizing | 0.906 | D | 0.375 | neutral | N | 0.474134397 | None | None | N |
| T/C | 0.4176 | ambiguous | 0.4318 | ambiguous | -0.597 | Destabilizing | 0.999 | D | 0.359 | neutral | None | None | None | None | N |
| T/D | 0.4957 | ambiguous | 0.4857 | ambiguous | -1.218 | Destabilizing | 0.969 | D | 0.376 | neutral | None | None | None | None | N |
| T/E | 0.4799 | ambiguous | 0.4641 | ambiguous | -1.208 | Destabilizing | 0.939 | D | 0.382 | neutral | None | None | None | None | N |
| T/F | 0.2664 | likely_benign | 0.2985 | benign | -0.843 | Destabilizing | 0.884 | D | 0.415 | neutral | None | None | None | None | N |
| T/G | 0.1977 | likely_benign | 0.1978 | benign | -0.877 | Destabilizing | 0.969 | D | 0.417 | neutral | None | None | None | None | N |
| T/H | 0.2427 | likely_benign | 0.2502 | benign | -1.273 | Destabilizing | 0.1 | N | 0.305 | neutral | None | None | None | None | N |
| T/I | 0.613 | likely_pathogenic | 0.6257 | pathogenic | -0.066 | Destabilizing | 0.988 | D | 0.369 | neutral | N | 0.508977009 | None | None | N |
| T/K | 0.2611 | likely_benign | 0.2366 | benign | -0.748 | Destabilizing | 0.969 | D | 0.385 | neutral | None | None | None | None | N |
| T/L | 0.1838 | likely_benign | 0.1873 | benign | -0.066 | Destabilizing | 0.939 | D | 0.38 | neutral | None | None | None | None | N |
| T/M | 0.1388 | likely_benign | 0.1319 | benign | 0.335 | Stabilizing | 0.999 | D | 0.353 | neutral | None | None | None | None | N |
| T/N | 0.1377 | likely_benign | 0.1412 | benign | -0.924 | Destabilizing | 0.92 | D | 0.394 | neutral | N | 0.470282829 | None | None | N |
| T/P | 0.816 | likely_pathogenic | 0.7762 | pathogenic | -0.223 | Destabilizing | 0.996 | D | 0.375 | neutral | D | 0.527081264 | None | None | N |
| T/Q | 0.2379 | likely_benign | 0.2325 | benign | -1.18 | Destabilizing | 0.991 | D | 0.377 | neutral | None | None | None | None | N |
| T/R | 0.2029 | likely_benign | 0.1798 | benign | -0.461 | Destabilizing | 0.991 | D | 0.366 | neutral | None | None | None | None | N |
| T/S | 0.1099 | likely_benign | 0.1123 | benign | -1.032 | Destabilizing | 0.959 | D | 0.405 | neutral | N | 0.44306111 | None | None | N |
| T/V | 0.4231 | ambiguous | 0.4409 | ambiguous | -0.223 | Destabilizing | 0.939 | D | 0.367 | neutral | None | None | None | None | N |
| T/W | 0.6093 | likely_pathogenic | 0.61 | pathogenic | -0.86 | Destabilizing | 0.998 | D | 0.382 | neutral | None | None | None | None | N |
| T/Y | 0.2615 | likely_benign | 0.2838 | benign | -0.544 | Destabilizing | 0.079 | N | 0.205 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.