Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33046 | 99361;99362;99363 | chr2:178538693;178538692;178538691 | chr2:179403420;179403419;179403418 |
| N2AB | 31405 | 94438;94439;94440 | chr2:178538693;178538692;178538691 | chr2:179403420;179403419;179403418 |
| N2A | 30478 | 91657;91658;91659 | chr2:178538693;178538692;178538691 | chr2:179403420;179403419;179403418 |
| N2B | 23981 | 72166;72167;72168 | chr2:178538693;178538692;178538691 | chr2:179403420;179403419;179403418 |
| Novex-1 | 24106 | 72541;72542;72543 | chr2:178538693;178538692;178538691 | chr2:179403420;179403419;179403418 |
| Novex-2 | 24173 | 72742;72743;72744 | chr2:178538693;178538692;178538691 | chr2:179403420;179403419;179403418 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs778078915  |
-0.219 | 1.0 | N | 0.733 | 0.303 | 0.207176502487 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| K/N | rs778078915 |
-0.219 | 1.0 | N | 0.733 | 0.303 | 0.207176502487 | gnomAD-4.0.0 | 1.59134E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8585E-06 | 0 | 0 |
| K/R | rs749815808 |
None | 0.999 | N | 0.611 | 0.355 | 0.349429436713 | gnomAD-4.0.0 | 2.05265E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69846E-06 | 0 | 0 |
| K/T | None | None | 1.0 | N | 0.717 | 0.529 | 0.344251166708 | gnomAD-4.0.0 | 6.84216E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99488E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.824 | likely_pathogenic | 0.8259 | pathogenic | -0.732 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| K/C | 0.8916 | likely_pathogenic | 0.8913 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/D | 0.9394 | likely_pathogenic | 0.9401 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| K/E | 0.5408 | ambiguous | 0.5057 | ambiguous | 0.035 | Stabilizing | 0.999 | D | 0.668 | neutral | N | 0.473306659 | None | None | N |
| K/F | 0.937 | likely_pathogenic | 0.9345 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| K/G | 0.8557 | likely_pathogenic | 0.8761 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| K/H | 0.562 | ambiguous | 0.5598 | ambiguous | -1.063 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| K/I | 0.651 | likely_pathogenic | 0.592 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| K/L | 0.6536 | likely_pathogenic | 0.6465 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| K/M | 0.5438 | ambiguous | 0.5212 | ambiguous | -0.09 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.45595305 | None | None | N |
| K/N | 0.8168 | likely_pathogenic | 0.8126 | pathogenic | -0.667 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.501375908 | None | None | N |
| K/P | 0.9882 | likely_pathogenic | 0.9904 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/Q | 0.2459 | likely_benign | 0.2406 | benign | -0.603 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.390765421 | None | None | N |
| K/R | 0.1036 | likely_benign | 0.1114 | benign | -0.44 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.446485418 | None | None | N |
| K/S | 0.8482 | likely_pathogenic | 0.8535 | pathogenic | -1.335 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| K/T | 0.5841 | likely_pathogenic | 0.5534 | ambiguous | -0.953 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.431131963 | None | None | N |
| K/V | 0.6198 | likely_pathogenic | 0.5677 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| K/W | 0.9287 | likely_pathogenic | 0.9337 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| K/Y | 0.8707 | likely_pathogenic | 0.8731 | pathogenic | 0.122 | Stabilizing | 1.0 | D | 0.701 | prob.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.