Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24888 | 74887;74888;74889 | chr2:178571470;178571469;178571468 | chr2:179436197;179436196;179436195 |
| N2AB | 23247 | 69964;69965;69966 | chr2:178571470;178571469;178571468 | chr2:179436197;179436196;179436195 |
| N2A | 22320 | 67183;67184;67185 | chr2:178571470;178571469;178571468 | chr2:179436197;179436196;179436195 |
| N2B | 15823 | 47692;47693;47694 | chr2:178571470;178571469;178571468 | chr2:179436197;179436196;179436195 |
| Novex-1 | 15948 | 48067;48068;48069 | chr2:178571470;178571469;178571468 | chr2:179436197;179436196;179436195 |
| Novex-2 | 16015 | 48268;48269;48270 | chr2:178571470;178571469;178571468 | chr2:179436197;179436196;179436195 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs1286127438  |
None | 0.892 | N | 0.521 | 0.265 | 0.247872288689 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1286127438 |
None | 0.892 | N | 0.521 | 0.265 | 0.247872288689 | gnomAD-4.0.0 | 6.57661E-06 | None | None | None | None | I | None | 2.41348E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs1708151139 |
None | 0.967 | N | 0.477 | 0.403 | 0.376216005999 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs1708151139 |
None | 0.967 | N | 0.477 | 0.403 | 0.376216005999 | gnomAD-4.0.0 | 5.57881E-06 | None | None | None | None | I | None | 9.34879E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20359E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9745 | likely_pathogenic | 0.9742 | pathogenic | 0.001 | Stabilizing | 0.845 | D | 0.56 | neutral | None | None | None | None | I |
| R/C | 0.8019 | likely_pathogenic | 0.8024 | pathogenic | -0.208 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| R/D | 0.9929 | likely_pathogenic | 0.9931 | pathogenic | -0.173 | Destabilizing | 0.975 | D | 0.53 | neutral | None | None | None | None | I |
| R/E | 0.9712 | likely_pathogenic | 0.9718 | pathogenic | -0.107 | Destabilizing | 0.845 | D | 0.537 | neutral | None | None | None | None | I |
| R/F | 0.9848 | likely_pathogenic | 0.9833 | pathogenic | -0.273 | Destabilizing | 0.996 | D | 0.58 | neutral | None | None | None | None | I |
| R/G | 0.9662 | likely_pathogenic | 0.9638 | pathogenic | -0.179 | Destabilizing | 0.892 | D | 0.464 | neutral | N | 0.508200306 | None | None | I |
| R/H | 0.6164 | likely_pathogenic | 0.6281 | pathogenic | -0.826 | Destabilizing | 0.987 | D | 0.509 | neutral | None | None | None | None | I |
| R/I | 0.9075 | likely_pathogenic | 0.9082 | pathogenic | 0.436 | Stabilizing | 0.983 | D | 0.585 | neutral | N | 0.503685495 | None | None | I |
| R/K | 0.4738 | ambiguous | 0.484 | ambiguous | -0.099 | Destabilizing | 0.025 | N | 0.358 | neutral | N | 0.471418361 | None | None | I |
| R/L | 0.903 | likely_pathogenic | 0.9027 | pathogenic | 0.436 | Stabilizing | 0.916 | D | 0.464 | neutral | None | None | None | None | I |
| R/M | 0.9466 | likely_pathogenic | 0.942 | pathogenic | -0.057 | Destabilizing | 0.999 | D | 0.491 | neutral | None | None | None | None | I |
| R/N | 0.9832 | likely_pathogenic | 0.9832 | pathogenic | 0.022 | Stabilizing | 0.975 | D | 0.493 | neutral | None | None | None | None | I |
| R/P | 0.9826 | likely_pathogenic | 0.9823 | pathogenic | 0.311 | Stabilizing | 0.987 | D | 0.543 | neutral | None | None | None | None | I |
| R/Q | 0.6086 | likely_pathogenic | 0.606 | pathogenic | -0.012 | Destabilizing | 0.975 | D | 0.496 | neutral | None | None | None | None | I |
| R/S | 0.9815 | likely_pathogenic | 0.9809 | pathogenic | -0.235 | Destabilizing | 0.892 | D | 0.521 | neutral | N | 0.482270072 | None | None | I |
| R/T | 0.9608 | likely_pathogenic | 0.961 | pathogenic | -0.037 | Destabilizing | 0.967 | D | 0.477 | neutral | N | 0.517036007 | None | None | I |
| R/V | 0.9525 | likely_pathogenic | 0.9521 | pathogenic | 0.311 | Stabilizing | 0.975 | D | 0.573 | neutral | None | None | None | None | I |
| R/W | 0.8308 | likely_pathogenic | 0.8205 | pathogenic | -0.407 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| R/Y | 0.9397 | likely_pathogenic | 0.9359 | pathogenic | 0.015 | Stabilizing | 0.996 | D | 0.551 | 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.