Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1602 | 5029;5030;5031 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
| N2AB | 1602 | 5029;5030;5031 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
| N2A | 1602 | 5029;5030;5031 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
| N2B | 1556 | 4891;4892;4893 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
| Novex-1 | 1556 | 4891;4892;4893 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
| Novex-2 | 1556 | 4891;4892;4893 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
| Novex-3 | 1602 | 5029;5030;5031 | chr2:178777159;178777158;178777157 | chr2:179641886;179641885;179641884 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | None | None | 1.0 | N | 0.58 | 0.601 | 0.52138495 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs2092321962  |
None | 1.0 | N | 0.492 | 0.492 | 0.43326968 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.232 | likely_benign | 0.2041 | benign | -0.555 | Destabilizing | 1.0 | D | 0.491 | neutral | D | 0.5495804 | None | None | I |
| P/C | 0.8877 | likely_pathogenic | 0.831 | pathogenic | -0.635 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| P/D | 0.7415 | likely_pathogenic | 0.6773 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.474 | neutral | None | None | None | None | I |
| P/E | 0.5247 | ambiguous | 0.454 | ambiguous | -0.645 | Destabilizing | 1.0 | D | 0.48 | neutral | None | None | None | None | I |
| P/F | 0.9174 | likely_pathogenic | 0.8764 | pathogenic | -0.675 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| P/G | 0.5518 | ambiguous | 0.4891 | ambiguous | -0.711 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | I |
| P/H | 0.4372 | ambiguous | 0.3769 | ambiguous | -0.269 | Destabilizing | 1.0 | D | 0.597 | neutral | N | 0.4940201 | None | None | I |
| P/I | 0.8141 | likely_pathogenic | 0.74 | pathogenic | -0.283 | Destabilizing | 1.0 | D | 0.626 | neutral | None | None | None | None | I |
| P/K | 0.5756 | likely_pathogenic | 0.494 | ambiguous | -0.627 | Destabilizing | 1.0 | D | 0.476 | neutral | None | None | None | None | I |
| P/L | 0.4401 | ambiguous | 0.3655 | ambiguous | -0.283 | Destabilizing | 1.0 | D | 0.6 | neutral | N | 0.48840207 | None | None | I |
| P/M | 0.7651 | likely_pathogenic | 0.6906 | pathogenic | -0.411 | Destabilizing | 1.0 | D | 0.605 | neutral | None | None | None | None | I |
| P/N | 0.6271 | likely_pathogenic | 0.5524 | ambiguous | -0.398 | Destabilizing | 1.0 | D | 0.586 | neutral | None | None | None | None | I |
| P/Q | 0.3084 | likely_benign | 0.2702 | benign | -0.614 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | I |
| P/R | 0.4129 | ambiguous | 0.3513 | ambiguous | -0.098 | Destabilizing | 1.0 | D | 0.58 | neutral | N | 0.5029619 | None | None | I |
| P/S | 0.2489 | likely_benign | 0.2124 | benign | -0.717 | Destabilizing | 1.0 | D | 0.492 | neutral | N | 0.50756717 | None | None | I |
| P/T | 0.3149 | likely_benign | 0.2598 | benign | -0.711 | Destabilizing | 1.0 | D | 0.483 | neutral | N | 0.5076525 | None | None | I |
| P/V | 0.6798 | likely_pathogenic | 0.5921 | pathogenic | -0.339 | Destabilizing | 1.0 | D | 0.537 | neutral | None | None | None | None | I |
| P/W | 0.9349 | likely_pathogenic | 0.9007 | pathogenic | -0.795 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| P/Y | 0.8675 | likely_pathogenic | 0.808 | pathogenic | -0.504 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
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.