Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28071 | 84436;84437;84438 | chr2:178561921;178561920;178561919 | chr2:179426648;179426647;179426646 |
| N2AB | 26430 | 79513;79514;79515 | chr2:178561921;178561920;178561919 | chr2:179426648;179426647;179426646 |
| N2A | 25503 | 76732;76733;76734 | chr2:178561921;178561920;178561919 | chr2:179426648;179426647;179426646 |
| N2B | 19006 | 57241;57242;57243 | chr2:178561921;178561920;178561919 | chr2:179426648;179426647;179426646 |
| Novex-1 | 19131 | 57616;57617;57618 | chr2:178561921;178561920;178561919 | chr2:179426648;179426647;179426646 |
| Novex-2 | 19198 | 57817;57818;57819 | chr2:178561921;178561920;178561919 | chr2:179426648;179426647;179426646 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs1489303376  |
-1.369 | None | N | 0.139 | 0.203 | 0.0401082797425 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| S/R | rs1169451357 |
-0.898 | 0.055 | N | 0.723 | 0.28 | 0.206339911435 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| S/R | rs1169451357 |
-0.898 | 0.055 | N | 0.723 | 0.28 | 0.206339911435 | gnomAD-4.0.0 | 1.59194E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85881E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1461 | likely_benign | 0.1421 | benign | -0.799 | Destabilizing | 0.014 | N | 0.375 | neutral | None | None | None | None | N |
| S/C | 0.085 | likely_benign | 0.0903 | benign | -1.103 | Destabilizing | 0.828 | D | 0.716 | prob.delet. | N | 0.507134265 | None | None | N |
| S/D | 0.4065 | ambiguous | 0.3826 | ambiguous | -1.838 | Destabilizing | 0.016 | N | 0.462 | neutral | None | None | None | None | N |
| S/E | 0.7025 | likely_pathogenic | 0.6933 | pathogenic | -1.752 | Destabilizing | 0.016 | N | 0.475 | neutral | None | None | None | None | N |
| S/F | 0.2802 | likely_benign | 0.2483 | benign | -1.031 | Destabilizing | None | N | 0.501 | neutral | None | None | None | None | N |
| S/G | 0.1198 | likely_benign | 0.1114 | benign | -1.06 | Destabilizing | 0.012 | N | 0.421 | neutral | N | 0.481508365 | None | None | N |
| S/H | 0.1749 | likely_benign | 0.1968 | benign | -1.457 | Destabilizing | 0.214 | N | 0.756 | deleterious | None | None | None | None | N |
| S/I | 0.298 | likely_benign | 0.2835 | benign | -0.187 | Destabilizing | 0.055 | N | 0.658 | neutral | D | 0.533378822 | None | None | N |
| S/K | 0.7339 | likely_pathogenic | 0.7287 | pathogenic | -0.713 | Destabilizing | 0.038 | N | 0.477 | neutral | None | None | None | None | N |
| S/L | 0.2628 | likely_benign | 0.2456 | benign | -0.187 | Destabilizing | 0.016 | N | 0.563 | neutral | None | None | None | None | N |
| S/M | 0.2615 | likely_benign | 0.2548 | benign | -0.102 | Destabilizing | 0.628 | D | 0.732 | prob.delet. | None | None | None | None | N |
| S/N | 0.079 | likely_benign | 0.0757 | benign | -1.212 | Destabilizing | None | N | 0.139 | neutral | N | 0.492611181 | None | None | N |
| S/P | 0.9757 | likely_pathogenic | 0.9648 | pathogenic | -0.36 | Destabilizing | 0.356 | N | 0.771 | deleterious | None | None | None | None | N |
| S/Q | 0.5155 | ambiguous | 0.5253 | ambiguous | -1.323 | Destabilizing | 0.072 | N | 0.623 | neutral | None | None | None | None | N |
| S/R | 0.6807 | likely_pathogenic | 0.6573 | pathogenic | -0.649 | Destabilizing | 0.055 | N | 0.723 | prob.delet. | N | 0.499359131 | None | None | N |
| S/T | 0.1086 | likely_benign | 0.1063 | benign | -0.958 | Destabilizing | 0.012 | N | 0.449 | neutral | N | 0.521487395 | None | None | N |
| S/V | 0.3161 | likely_benign | 0.3102 | benign | -0.36 | Destabilizing | 0.072 | N | 0.625 | neutral | None | None | None | None | N |
| S/W | 0.4922 | ambiguous | 0.4714 | ambiguous | -1.164 | Destabilizing | 0.356 | N | 0.721 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1466 | likely_benign | 0.1517 | benign | -0.76 | Destabilizing | None | N | 0.527 | 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.