Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15083 | 45472;45473;45474 | chr2:178621577;178621576;178621575 | chr2:179486304;179486303;179486302 |
| N2AB | 13442 | 40549;40550;40551 | chr2:178621577;178621576;178621575 | chr2:179486304;179486303;179486302 |
| N2A | 12515 | 37768;37769;37770 | chr2:178621577;178621576;178621575 | chr2:179486304;179486303;179486302 |
| N2B | 6018 | 18277;18278;18279 | chr2:178621577;178621576;178621575 | chr2:179486304;179486303;179486302 |
| Novex-1 | 6143 | 18652;18653;18654 | chr2:178621577;178621576;178621575 | chr2:179486304;179486303;179486302 |
| Novex-2 | 6210 | 18853;18854;18855 | chr2:178621577;178621576;178621575 | chr2:179486304;179486303;179486302 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | rs191551032  |
None | 0.999 | N | 0.725 | 0.334 | 0.565391359567 | gnomAD-4.0.0 | 3.4234E-06 | None | None | None | None | N | None | 2.99276E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59971E-06 | 0 | 0 |
| R/Q | rs191551032 |
-0.383 | 0.998 | N | 0.658 | 0.23 | None | gnomAD-2.1.1 | 4.84E-05 | None | None | None | None | N | None | 1.29316E-04 | 2.91E-05 | None | 0 | 1.12435E-04 | None | 1.63452E-04 | None | 0 | 8.93E-06 | 1.66445E-04 |
| R/Q | rs191551032 |
-0.383 | 0.998 | N | 0.658 | 0.23 | None | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs191551032 |
-0.383 | 0.998 | N | 0.658 | 0.23 | None | gnomAD-4.0.0 | 2.29483E-05 | None | None | None | None | N | None | 5.34845E-05 | 5.01354E-05 | None | 0 | 2.23944E-05 | None | 0 | 0 | 1.61143E-05 | 9.88424E-05 | 1.60287E-05 |
| R/W | rs199834143 |
-0.464 | 1.0 | D | 0.739 | 0.493 | None | gnomAD-2.1.1 | 7.52E-05 | None | None | None | None | N | None | 8.27E-05 | 1.1352E-04 | None | 0 | 5.18E-05 | None | 3.27E-05 | None | 0 | 9.42E-05 | 1.40924E-04 |
| R/W | rs199834143 |
-0.464 | 1.0 | D | 0.739 | 0.493 | None | gnomAD-3.1.2 | 9.23E-05 | None | None | None | None | N | None | 9.68E-05 | 1.97291E-04 | 0 | 0 | 0 | None | 0 | 0 | 8.84E-05 | 2.07211E-04 | 0 |
| R/W | rs199834143 |
-0.464 | 1.0 | D | 0.739 | 0.493 | None | gnomAD-4.0.0 | 1.01719E-04 | None | None | None | None | N | None | 6.68861E-05 | 1.17006E-04 | None | 0 | 4.47708E-05 | None | 0 | 0 | 1.15343E-04 | 5.49101E-05 | 1.44254E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4757 | ambiguous | 0.5958 | pathogenic | -0.851 | Destabilizing | 0.97 | D | 0.653 | neutral | None | None | None | None | N |
| R/C | 0.2741 | likely_benign | 0.3564 | ambiguous | -0.804 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| R/D | 0.7142 | likely_pathogenic | 0.8031 | pathogenic | -0.15 | Destabilizing | 0.996 | D | 0.663 | neutral | None | None | None | None | N |
| R/E | 0.4367 | ambiguous | 0.5057 | ambiguous | -0.062 | Destabilizing | 0.97 | D | 0.637 | neutral | None | None | None | None | N |
| R/F | 0.6834 | likely_pathogenic | 0.7575 | pathogenic | -0.905 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/G | 0.2481 | likely_benign | 0.318 | benign | -1.112 | Destabilizing | 0.992 | D | 0.645 | neutral | N | 0.491373051 | None | None | N |
| R/H | 0.1523 | likely_benign | 0.1823 | benign | -1.367 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| R/I | 0.4028 | ambiguous | 0.4723 | ambiguous | -0.163 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/K | 0.0979 | likely_benign | 0.1086 | benign | -0.896 | Destabilizing | 0.155 | N | 0.243 | neutral | None | None | None | None | N |
| R/L | 0.3375 | likely_benign | 0.431 | ambiguous | -0.163 | Destabilizing | 0.992 | D | 0.645 | neutral | N | 0.511407629 | None | None | N |
| R/M | 0.349 | ambiguous | 0.4311 | ambiguous | -0.341 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/N | 0.5613 | ambiguous | 0.6865 | pathogenic | -0.29 | Destabilizing | 0.996 | D | 0.627 | neutral | None | None | None | None | N |
| R/P | 0.5367 | ambiguous | 0.6322 | pathogenic | -0.373 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | N | 0.51100084 | None | None | N |
| R/Q | 0.1191 | likely_benign | 0.1175 | benign | -0.561 | Destabilizing | 0.998 | D | 0.658 | neutral | N | 0.500444872 | None | None | N |
| R/S | 0.5285 | ambiguous | 0.6514 | pathogenic | -1.064 | Destabilizing | 0.97 | D | 0.671 | neutral | None | None | None | None | N |
| R/T | 0.336 | likely_benign | 0.4506 | ambiguous | -0.816 | Destabilizing | 0.985 | D | 0.65 | neutral | None | None | None | None | N |
| R/V | 0.5129 | ambiguous | 0.6031 | pathogenic | -0.373 | Destabilizing | 0.996 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/W | 0.2422 | likely_benign | 0.2661 | benign | -0.596 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.591784175 | None | None | N |
| R/Y | 0.5168 | ambiguous | 0.6095 | pathogenic | -0.283 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | 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.