Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1785 | 5578;5579;5580 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
| N2AB | 1785 | 5578;5579;5580 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
| N2A | 1785 | 5578;5579;5580 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
| N2B | 1739 | 5440;5441;5442 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
| Novex-1 | 1739 | 5440;5441;5442 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
| Novex-2 | 1739 | 5440;5441;5442 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
| Novex-3 | 1785 | 5578;5579;5580 | chr2:178776511;178776510;178776509 | chr2:179641238;179641237;179641236 |
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/I | rs397517649  |
0.003 | 0.134 | N | 0.204 | 0.242 | 0.388495093706 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs397517649 |
0.003 | 0.134 | N | 0.204 | 0.242 | 0.388495093706 | gnomAD-4.0.0 | 6.86515E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15931E-05 | 0 |
| T/R | rs397517649 |
-0.344 | 0.988 | N | 0.487 | 0.315 | 0.640464653361 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| T/R | rs397517649 |
-0.344 | 0.988 | N | 0.487 | 0.315 | 0.640464653361 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/R | rs397517649 |
-0.344 | 0.988 | N | 0.487 | 0.315 | 0.640464653361 | gnomAD-4.0.0 | 3.10791E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23734E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1194 | likely_benign | 0.1345 | benign | -0.551 | Destabilizing | 0.061 | N | 0.102 | neutral | N | 0.482950403 | None | None | I |
| T/C | 0.6654 | likely_pathogenic | 0.6561 | pathogenic | -0.17 | Destabilizing | 0.997 | D | 0.483 | neutral | None | None | None | None | I |
| T/D | 0.6775 | likely_pathogenic | 0.7356 | pathogenic | -0.24 | Destabilizing | 0.991 | D | 0.446 | neutral | None | None | None | None | I |
| T/E | 0.4947 | ambiguous | 0.5705 | pathogenic | -0.3 | Destabilizing | 0.969 | D | 0.456 | neutral | None | None | None | None | I |
| T/F | 0.51 | ambiguous | 0.5848 | pathogenic | -0.849 | Destabilizing | 0.991 | D | 0.585 | neutral | None | None | None | None | I |
| T/G | 0.4377 | ambiguous | 0.4563 | ambiguous | -0.735 | Destabilizing | 0.884 | D | 0.567 | neutral | None | None | None | None | I |
| T/H | 0.5008 | ambiguous | 0.5368 | ambiguous | -1.028 | Destabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | I |
| T/I | 0.2704 | likely_benign | 0.3469 | ambiguous | -0.167 | Destabilizing | 0.134 | N | 0.204 | neutral | N | 0.512988263 | None | None | I |
| T/K | 0.4634 | ambiguous | 0.5121 | ambiguous | -0.604 | Destabilizing | 0.92 | D | 0.446 | neutral | N | 0.468510074 | None | None | I |
| T/L | 0.2263 | likely_benign | 0.2745 | benign | -0.167 | Destabilizing | 0.759 | D | 0.442 | neutral | None | None | None | None | I |
| T/M | 0.1339 | likely_benign | 0.1609 | benign | 0.202 | Stabilizing | 0.991 | D | 0.485 | neutral | None | None | None | None | I |
| T/N | 0.2221 | likely_benign | 0.2507 | benign | -0.316 | Destabilizing | 0.997 | D | 0.421 | neutral | None | None | None | None | I |
| T/P | 0.6876 | likely_pathogenic | 0.7133 | pathogenic | -0.265 | Destabilizing | 0.988 | D | 0.466 | neutral | D | 0.55516313 | None | None | I |
| T/Q | 0.3529 | ambiguous | 0.3962 | ambiguous | -0.589 | Destabilizing | 0.997 | D | 0.491 | neutral | None | None | None | None | I |
| T/R | 0.4352 | ambiguous | 0.4759 | ambiguous | -0.246 | Destabilizing | 0.988 | D | 0.487 | neutral | N | 0.50053257 | None | None | I |
| T/S | 0.1426 | likely_benign | 0.153 | benign | -0.527 | Destabilizing | 0.704 | D | 0.349 | neutral | N | 0.437266986 | None | None | I |
| T/V | 0.185 | likely_benign | 0.2184 | benign | -0.265 | Destabilizing | 0.079 | N | 0.103 | neutral | None | None | None | None | I |
| T/W | 0.865 | likely_pathogenic | 0.8832 | pathogenic | -0.813 | Destabilizing | 0.999 | D | 0.594 | neutral | None | None | None | None | I |
| T/Y | 0.6039 | likely_pathogenic | 0.6335 | pathogenic | -0.581 | Destabilizing | 0.997 | D | 0.595 | 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.