Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2327 | 7204;7205;7206 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
| N2AB | 2327 | 7204;7205;7206 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
| N2A | 2327 | 7204;7205;7206 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
| N2B | 2281 | 7066;7067;7068 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
| Novex-1 | 2281 | 7066;7067;7068 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
| Novex-2 | 2281 | 7066;7067;7068 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
| Novex-3 | 2327 | 7204;7205;7206 | chr2:178774285;178774284;178774283 | chr2:179639012;179639011;179639010 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1342961134  |
-0.395 | 1.0 | N | 0.653 | 0.539 | 0.181679512989 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| D/G | rs1342961134 |
-0.395 | 1.0 | N | 0.653 | 0.539 | 0.181679512989 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/G | rs1342961134 |
-0.395 | 1.0 | N | 0.653 | 0.539 | 0.181679512989 | gnomAD-4.0.0 | 6.19565E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47455E-06 | 0 | 0 |
| D/V | None | None | 1.0 | N | 0.729 | 0.635 | 0.488337271218 | gnomAD-4.0.0 | 6.84082E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99313E-07 | 0 | 0 |
| D/Y | rs1554002409 |
None | 1.0 | D | 0.683 | 0.637 | 0.555395099047 | 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 |
| D/Y | rs1554002409 |
None | 1.0 | D | 0.683 | 0.637 | 0.555395099047 | gnomAD-4.0.0 | 2.02994E-06 | None | None | None | None | N | None | 1.7474E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20493E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4495 | ambiguous | 0.4858 | ambiguous | -0.44 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.48674289 | None | None | N |
| D/C | 0.9074 | likely_pathogenic | 0.9249 | pathogenic | 0.134 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/E | 0.3265 | likely_benign | 0.357 | ambiguous | -0.408 | Destabilizing | 1.0 | D | 0.457 | neutral | N | 0.43757701 | None | None | N |
| D/F | 0.8243 | likely_pathogenic | 0.8467 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/G | 0.3379 | likely_benign | 0.3654 | ambiguous | -0.65 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.442215036 | None | None | N |
| D/H | 0.7053 | likely_pathogenic | 0.7344 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.642 | neutral | N | 0.477281316 | None | None | N |
| D/I | 0.7958 | likely_pathogenic | 0.8292 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/K | 0.8359 | likely_pathogenic | 0.8505 | pathogenic | 0.201 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/L | 0.7481 | likely_pathogenic | 0.7727 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/M | 0.8596 | likely_pathogenic | 0.8806 | pathogenic | 0.47 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/N | 0.1839 | likely_benign | 0.1946 | benign | -0.031 | Destabilizing | 1.0 | D | 0.624 | neutral | N | 0.441205696 | None | None | N |
| D/P | 0.9741 | likely_pathogenic | 0.9822 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/Q | 0.7506 | likely_pathogenic | 0.7744 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| D/R | 0.8548 | likely_pathogenic | 0.87 | pathogenic | 0.197 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/S | 0.359 | ambiguous | 0.3856 | ambiguous | -0.17 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| D/T | 0.6231 | likely_pathogenic | 0.6675 | pathogenic | -0.007 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/V | 0.5954 | likely_pathogenic | 0.6403 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.49054091 | None | None | N |
| D/W | 0.9675 | likely_pathogenic | 0.9728 | pathogenic | -0.467 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/Y | 0.4339 | ambiguous | 0.4539 | ambiguous | -0.337 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | D | 0.57249396 | 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.