Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5463 | 16612;16613;16614 | chr2:178732674;178732673;178732672 | chr2:179597401;179597400;179597399 |
| N2AB | 5146 | 15661;15662;15663 | chr2:178732674;178732673;178732672 | chr2:179597401;179597400;179597399 |
| N2A | 4219 | 12880;12881;12882 | chr2:178732674;178732673;178732672 | chr2:179597401;179597400;179597399 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs748705824  |
-0.65 | 1.0 | N | 0.759 | 0.351 | 0.156986980423 | gnomAD-2.1.1 | 4.14E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.45E-05 | None | 0 | 0 | 0 |
| P/S | rs748705824 |
-0.65 | 1.0 | N | 0.759 | 0.351 | 0.156986980423 | gnomAD-4.0.0 | 1.37516E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.17553E-05 | 1.66628E-05 |
| P/T | rs748705824 |
-0.596 | 1.0 | N | 0.753 | 0.349 | 0.266843984389 | gnomAD-2.1.1 | 8.28E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.89E-05 | None | 0 | 0 | 0 |
| P/T | rs748705824 |
-0.596 | 1.0 | N | 0.753 | 0.349 | 0.266843984389 | gnomAD-4.0.0 | 1.37516E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.35106E-05 | 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 | 0.1236 | likely_benign | 0.142 | benign | -0.847 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.446066051 | None | None | I |
| P/C | 0.6608 | likely_pathogenic | 0.7594 | pathogenic | -0.801 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| P/D | 0.746 | likely_pathogenic | 0.8576 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| P/E | 0.4148 | ambiguous | 0.5321 | ambiguous | -0.39 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| P/F | 0.597 | likely_pathogenic | 0.7728 | pathogenic | -0.736 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| P/G | 0.5192 | ambiguous | 0.6323 | pathogenic | -1.069 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| P/H | 0.3581 | ambiguous | 0.5022 | ambiguous | -0.527 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.474441479 | None | None | I |
| P/I | 0.3338 | likely_benign | 0.444 | ambiguous | -0.387 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| P/K | 0.481 | ambiguous | 0.6407 | pathogenic | -0.722 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| P/L | 0.1311 | likely_benign | 0.1936 | benign | -0.387 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.469289627 | None | None | I |
| P/M | 0.4164 | ambiguous | 0.5373 | ambiguous | -0.411 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| P/N | 0.6135 | likely_pathogenic | 0.7459 | pathogenic | -0.502 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | I |
| P/Q | 0.2635 | likely_benign | 0.3691 | ambiguous | -0.698 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| P/R | 0.2947 | likely_benign | 0.4332 | ambiguous | -0.209 | Destabilizing | 1.0 | D | 0.829 | deleterious | N | 0.502018121 | None | None | I |
| P/S | 0.2409 | likely_benign | 0.3114 | benign | -0.993 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.444375327 | None | None | I |
| P/T | 0.1742 | likely_benign | 0.2325 | benign | -0.946 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.454706964 | None | None | I |
| P/V | 0.2474 | likely_benign | 0.3138 | benign | -0.503 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| P/W | 0.7304 | likely_pathogenic | 0.8575 | pathogenic | -0.83 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| P/Y | 0.5974 | likely_pathogenic | 0.7433 | pathogenic | -0.543 | Destabilizing | 1.0 | D | 0.799 | deleterious | 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.