Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16764 | 50515;50516;50517 | chr2:178612121;178612120;178612119 | chr2:179476848;179476847;179476846 |
| N2AB | 15123 | 45592;45593;45594 | chr2:178612121;178612120;178612119 | chr2:179476848;179476847;179476846 |
| N2A | 14196 | 42811;42812;42813 | chr2:178612121;178612120;178612119 | chr2:179476848;179476847;179476846 |
| N2B | 7699 | 23320;23321;23322 | chr2:178612121;178612120;178612119 | chr2:179476848;179476847;179476846 |
| Novex-1 | 7824 | 23695;23696;23697 | chr2:178612121;178612120;178612119 | chr2:179476848;179476847;179476846 |
| Novex-2 | 7891 | 23896;23897;23898 | chr2:178612121;178612120;178612119 | chr2:179476848;179476847;179476846 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.76 | N | 0.441 | 0.263 | 0.332902724076 | gnomAD-4.0.0 | 1.59528E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79626E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs748125248  |
0.305 | 0.991 | D | 0.491 | 0.402 | 0.50143340055 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| T/I | rs748125248 |
0.305 | 0.991 | D | 0.491 | 0.402 | 0.50143340055 | gnomAD-4.0.0 | 2.05492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.48529E-05 | 0 |
| T/S | None | None | 0.374 | N | 0.314 | 0.179 | 0.218845423259 | gnomAD-4.0.0 | 3.19057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.87233E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3473 | ambiguous | 0.3757 | ambiguous | -0.757 | Destabilizing | 0.76 | D | 0.441 | neutral | N | 0.487450529 | None | None | N |
| T/C | 0.7737 | likely_pathogenic | 0.7705 | pathogenic | -0.571 | Destabilizing | 0.999 | D | 0.487 | neutral | None | None | None | None | N |
| T/D | 0.6824 | likely_pathogenic | 0.7188 | pathogenic | -1.362 | Destabilizing | 0.986 | D | 0.441 | neutral | None | None | None | None | N |
| T/E | 0.7589 | likely_pathogenic | 0.7998 | pathogenic | -1.256 | Destabilizing | 0.91 | D | 0.449 | neutral | None | None | None | None | N |
| T/F | 0.7919 | likely_pathogenic | 0.823 | pathogenic | -0.425 | Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | None | N |
| T/G | 0.3874 | ambiguous | 0.4123 | ambiguous | -1.123 | Destabilizing | 0.953 | D | 0.463 | neutral | None | None | None | None | N |
| T/H | 0.6085 | likely_pathogenic | 0.6126 | pathogenic | -1.519 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | N |
| T/I | 0.8384 | likely_pathogenic | 0.8871 | pathogenic | 0.164 | Stabilizing | 0.991 | D | 0.491 | neutral | D | 0.563011154 | None | None | N |
| T/K | 0.5742 | likely_pathogenic | 0.6383 | pathogenic | -1.045 | Destabilizing | 0.1 | N | 0.339 | neutral | N | 0.479806484 | None | None | N |
| T/L | 0.4906 | ambiguous | 0.5491 | ambiguous | 0.164 | Stabilizing | 0.953 | D | 0.435 | neutral | None | None | None | None | N |
| T/M | 0.3738 | ambiguous | 0.3974 | ambiguous | 0.328 | Stabilizing | 0.999 | D | 0.476 | neutral | None | None | None | None | N |
| T/N | 0.2503 | likely_benign | 0.2733 | benign | -1.384 | Destabilizing | 0.986 | D | 0.466 | neutral | None | None | None | None | N |
| T/P | 0.7746 | likely_pathogenic | 0.8322 | pathogenic | -0.109 | Destabilizing | 0.991 | D | 0.492 | neutral | D | 0.627109391 | None | None | N |
| T/Q | 0.538 | ambiguous | 0.587 | pathogenic | -1.285 | Destabilizing | 0.986 | D | 0.492 | neutral | None | None | None | None | N |
| T/R | 0.5519 | ambiguous | 0.6279 | pathogenic | -1.08 | Destabilizing | 0.964 | D | 0.44 | neutral | N | 0.488509449 | None | None | N |
| T/S | 0.1643 | likely_benign | 0.1596 | benign | -1.459 | Destabilizing | 0.374 | N | 0.314 | neutral | N | 0.435441614 | None | None | N |
| T/V | 0.6733 | likely_pathogenic | 0.7427 | pathogenic | -0.109 | Destabilizing | 0.976 | D | 0.427 | neutral | None | None | None | None | N |
| T/W | 0.9158 | likely_pathogenic | 0.9277 | pathogenic | -0.616 | Destabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | N |
| T/Y | 0.809 | likely_pathogenic | 0.8356 | pathogenic | -0.309 | Destabilizing | 0.998 | D | 0.575 | 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.