Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6939 | 21040;21041;21042 | chr2:178725389;178725388;178725387 | chr2:179590116;179590115;179590114 |
| N2AB | 6622 | 20089;20090;20091 | chr2:178725389;178725388;178725387 | chr2:179590116;179590115;179590114 |
| N2A | 5695 | 17308;17309;17310 | chr2:178725389;178725388;178725387 | chr2:179590116;179590115;179590114 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs748115880  |
-0.175 | None | N | 0.117 | 0.18 | 0.419090007872 | gnomAD-2.1.1 | 4.62E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.09E-05 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs748115880 |
-0.175 | None | N | 0.117 | 0.18 | 0.419090007872 | gnomAD-4.0.0 | 1.6711E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.81389E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | None | None | None | N | 0.101 | 0.102 | 0.466571191598 | gnomAD-4.0.0 | 6.96892E-07 | None | None | None | None | N | None | 3.01514E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | None | None | None | N | 0.175 | 0.158 | 0.636139071576 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/V | None | None | None | N | 0.167 | 0.112 | 0.318540980066 | gnomAD-4.0.0 | 2.78757E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.6454E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1826 | likely_benign | 0.1697 | benign | -1.354 | Destabilizing | 0.002 | N | 0.215 | neutral | None | None | None | None | N |
| M/C | 0.6309 | likely_pathogenic | 0.6349 | pathogenic | -0.909 | Destabilizing | 0.497 | N | 0.492 | neutral | None | None | None | None | N |
| M/D | 0.6407 | likely_pathogenic | 0.6202 | pathogenic | -0.265 | Destabilizing | 0.009 | N | 0.399 | neutral | None | None | None | None | N |
| M/E | 0.3487 | ambiguous | 0.3282 | benign | -0.274 | Destabilizing | None | N | 0.267 | neutral | None | None | None | None | N |
| M/F | 0.2198 | likely_benign | 0.2041 | benign | -0.579 | Destabilizing | 0.009 | N | 0.355 | neutral | None | None | None | None | N |
| M/G | 0.4098 | ambiguous | 0.3766 | ambiguous | -1.619 | Destabilizing | 0.018 | N | 0.373 | neutral | None | None | None | None | N |
| M/H | 0.3146 | likely_benign | 0.3003 | benign | -0.685 | Destabilizing | 0.497 | N | 0.541 | neutral | None | None | None | None | N |
| M/I | 0.1701 | likely_benign | 0.1625 | benign | -0.702 | Destabilizing | None | N | 0.117 | neutral | N | 0.400340201 | None | None | N |
| M/K | 0.16 | likely_benign | 0.1483 | benign | -0.249 | Destabilizing | 0.006 | N | 0.305 | neutral | N | 0.408263464 | None | None | N |
| M/L | 0.1147 | likely_benign | 0.1116 | benign | -0.702 | Destabilizing | None | N | 0.101 | neutral | N | 0.437781082 | None | None | N |
| M/N | 0.2955 | likely_benign | 0.2766 | benign | -0.064 | Destabilizing | 0.018 | N | 0.423 | neutral | None | None | None | None | N |
| M/P | 0.6459 | likely_pathogenic | 0.6248 | pathogenic | -0.891 | Destabilizing | 0.085 | N | 0.483 | neutral | None | None | None | None | N |
| M/Q | 0.1857 | likely_benign | 0.1774 | benign | -0.204 | Destabilizing | 0.018 | N | 0.358 | neutral | None | None | None | None | N |
| M/R | 0.1628 | likely_benign | 0.1495 | benign | 0.28 | Stabilizing | 0.014 | N | 0.403 | neutral | N | 0.41805917 | None | None | N |
| M/S | 0.1773 | likely_benign | 0.1666 | benign | -0.623 | Destabilizing | None | N | 0.173 | neutral | None | None | None | None | N |
| M/T | 0.086 | likely_benign | 0.0836 | benign | -0.525 | Destabilizing | None | N | 0.175 | neutral | N | 0.358933509 | None | None | N |
| M/V | 0.0635 | likely_benign | 0.0625 | benign | -0.891 | Destabilizing | None | N | 0.167 | neutral | N | 0.405015302 | None | None | N |
| M/W | 0.4705 | ambiguous | 0.4607 | ambiguous | -0.495 | Destabilizing | 0.497 | N | 0.497 | neutral | None | None | None | None | N |
| M/Y | 0.3966 | ambiguous | 0.3821 | ambiguous | -0.479 | Destabilizing | 0.085 | N | 0.473 | 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.