Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27084 | 81475;81476;81477 | chr2:178564882;178564881;178564880 | chr2:179429609;179429608;179429607 |
| N2AB | 25443 | 76552;76553;76554 | chr2:178564882;178564881;178564880 | chr2:179429609;179429608;179429607 |
| N2A | 24516 | 73771;73772;73773 | chr2:178564882;178564881;178564880 | chr2:179429609;179429608;179429607 |
| N2B | 18019 | 54280;54281;54282 | chr2:178564882;178564881;178564880 | chr2:179429609;179429608;179429607 |
| Novex-1 | 18144 | 54655;54656;54657 | chr2:178564882;178564881;178564880 | chr2:179429609;179429608;179429607 |
| Novex-2 | 18211 | 54856;54857;54858 | chr2:178564882;178564881;178564880 | chr2:179429609;179429608;179429607 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs371498697  |
None | 0.055 | N | 0.316 | 0.165 | 0.126345400529 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/F | rs371498697 |
None | 0.055 | N | 0.316 | 0.165 | 0.126345400529 | gnomAD-4.0.0 | 1.24041E-06 | None | None | None | None | N | None | 2.6733E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs371498697 |
-1.1 | None | N | 0.069 | 0.13 | None | gnomAD-2.1.1 | 3.25E-05 | None | None | None | None | N | None | 3.23666E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 1.67898E-04 |
| I/V | rs371498697 |
-1.1 | None | N | 0.069 | 0.13 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 1.92957E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs371498697 |
-1.1 | None | N | 0.069 | 0.13 | None | gnomAD-4.0.0 | 3.47314E-05 | None | None | None | None | N | None | 2.00497E-04 | 1.67274E-05 | None | 0 | 0 | None | 0 | 0 | 3.30674E-05 | 0 | 1.60339E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1288 | likely_benign | 0.1464 | benign | -1.85 | Destabilizing | None | N | 0.105 | neutral | None | None | None | None | N |
| I/C | 0.3487 | ambiguous | 0.3424 | ambiguous | -1.281 | Destabilizing | 0.356 | N | 0.352 | neutral | None | None | None | None | N |
| I/D | 0.6127 | likely_pathogenic | 0.6241 | pathogenic | -1.555 | Destabilizing | 0.136 | N | 0.489 | neutral | None | None | None | None | N |
| I/E | 0.5302 | ambiguous | 0.5478 | ambiguous | -1.546 | Destabilizing | 0.072 | N | 0.403 | neutral | None | None | None | None | N |
| I/F | 0.1491 | likely_benign | 0.145 | benign | -1.525 | Destabilizing | 0.055 | N | 0.316 | neutral | N | 0.493799362 | None | None | N |
| I/G | 0.3893 | ambiguous | 0.4053 | ambiguous | -2.181 | Highly Destabilizing | 0.016 | N | 0.346 | neutral | None | None | None | None | N |
| I/H | 0.3861 | ambiguous | 0.3912 | ambiguous | -1.517 | Destabilizing | 0.864 | D | 0.363 | neutral | None | None | None | None | N |
| I/K | 0.2887 | likely_benign | 0.3087 | benign | -1.171 | Destabilizing | 0.072 | N | 0.405 | neutral | None | None | None | None | N |
| I/L | 0.1003 | likely_benign | 0.0983 | benign | -1.0 | Destabilizing | None | N | 0.084 | neutral | N | 0.461185511 | None | None | N |
| I/M | 0.1051 | likely_benign | 0.1036 | benign | -0.777 | Destabilizing | 0.171 | N | 0.377 | neutral | N | 0.515366713 | None | None | N |
| I/N | 0.1969 | likely_benign | 0.2033 | benign | -1.036 | Destabilizing | 0.295 | N | 0.473 | neutral | N | 0.475398164 | None | None | N |
| I/P | 0.6037 | likely_pathogenic | 0.6634 | pathogenic | -1.254 | Destabilizing | 0.136 | N | 0.492 | neutral | None | None | None | None | N |
| I/Q | 0.3319 | likely_benign | 0.3475 | ambiguous | -1.242 | Destabilizing | 0.356 | N | 0.455 | neutral | None | None | None | None | N |
| I/R | 0.2185 | likely_benign | 0.2327 | benign | -0.621 | Destabilizing | 0.356 | N | 0.485 | neutral | None | None | None | None | N |
| I/S | 0.1434 | likely_benign | 0.1483 | benign | -1.66 | Destabilizing | 0.012 | N | 0.307 | neutral | N | 0.439599518 | None | None | N |
| I/T | 0.112 | likely_benign | 0.117 | benign | -1.533 | Destabilizing | 0.012 | N | 0.353 | neutral | N | 0.474192094 | None | None | N |
| I/V | 0.0534 | likely_benign | 0.0543 | benign | -1.254 | Destabilizing | None | N | 0.069 | neutral | N | 0.398787471 | None | None | N |
| I/W | 0.7705 | likely_pathogenic | 0.7526 | pathogenic | -1.624 | Destabilizing | 0.864 | D | 0.391 | neutral | None | None | None | None | N |
| I/Y | 0.4143 | ambiguous | 0.4072 | ambiguous | -1.358 | Destabilizing | 0.356 | N | 0.467 | 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.