Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8388 | 25387;25388;25389 | chr2:178717712;178717711;178717710 | chr2:179582439;179582438;179582437 |
| N2AB | 8071 | 24436;24437;24438 | chr2:178717712;178717711;178717710 | chr2:179582439;179582438;179582437 |
| N2A | 7144 | 21655;21656;21657 | chr2:178717712;178717711;178717710 | chr2:179582439;179582438;179582437 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.974 | D | 0.561 | 0.394 | 0.40032279838 | gnomAD-4.0.0 | 6.8438E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99617E-07 | 0 | 0 |
| P/L | rs745902643  |
0.17 | 1.0 | N | 0.681 | 0.447 | 0.732157991247 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs745902643 |
0.17 | 1.0 | N | 0.681 | 0.447 | 0.732157991247 | gnomAD-4.0.0 | 4.10631E-06 | None | None | None | None | I | None | 5.97764E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59847E-06 | 0 | 0 |
| P/R | None | None | 1.0 | N | 0.677 | 0.421 | 0.551961605406 | gnomAD-4.0.0 | 4.79069E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29733E-06 | 0 | 0 |
| P/S | rs727503647 |
-0.015 | 0.958 | N | 0.426 | 0.434 | 0.40218521252 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | I | None | 0 | 1.45315E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs727503647 |
-0.015 | 0.958 | N | 0.426 | 0.434 | 0.40218521252 | gnomAD-4.0.0 | 4.10628E-06 | None | None | None | None | I | None | 0 | 1.34228E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs727503647 |
None | 0.995 | D | 0.623 | 0.39 | 0.46123363591 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/T | rs727503647 |
None | 0.995 | D | 0.623 | 0.39 | 0.46123363591 | gnomAD-4.0.0 | 2.4794E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54325E-06 | 0 | 1.60185E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2814 | likely_benign | 0.2708 | benign | -0.582 | Destabilizing | 0.974 | D | 0.561 | neutral | D | 0.531152603 | None | None | I |
| P/C | 0.8971 | likely_pathogenic | 0.901 | pathogenic | -0.563 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| P/D | 0.5858 | likely_pathogenic | 0.611 | pathogenic | -0.434 | Destabilizing | 0.988 | D | 0.626 | neutral | None | None | None | None | I |
| P/E | 0.5315 | ambiguous | 0.5449 | ambiguous | -0.552 | Destabilizing | 0.992 | D | 0.628 | neutral | None | None | None | None | I |
| P/F | 0.822 | likely_pathogenic | 0.846 | pathogenic | -0.807 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| P/G | 0.6297 | likely_pathogenic | 0.6428 | pathogenic | -0.722 | Destabilizing | 0.996 | D | 0.617 | neutral | None | None | None | None | I |
| P/H | 0.5303 | ambiguous | 0.5403 | ambiguous | -0.322 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.519712474 | None | None | I |
| P/I | 0.6286 | likely_pathogenic | 0.6561 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| P/K | 0.664 | likely_pathogenic | 0.6647 | pathogenic | -0.529 | Destabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | I |
| P/L | 0.3637 | ambiguous | 0.3887 | ambiguous | -0.363 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.499531077 | None | None | I |
| P/M | 0.6506 | likely_pathogenic | 0.6669 | pathogenic | -0.347 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| P/N | 0.5452 | ambiguous | 0.555 | ambiguous | -0.189 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | I |
| P/Q | 0.4635 | ambiguous | 0.4613 | ambiguous | -0.461 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | I |
| P/R | 0.5228 | ambiguous | 0.5252 | ambiguous | 0.019 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.485376842 | None | None | I |
| P/S | 0.3932 | ambiguous | 0.3816 | ambiguous | -0.537 | Destabilizing | 0.958 | D | 0.426 | neutral | N | 0.490212234 | None | None | I |
| P/T | 0.325 | likely_benign | 0.3179 | benign | -0.558 | Destabilizing | 0.995 | D | 0.623 | neutral | D | 0.532518039 | None | None | I |
| P/V | 0.4919 | ambiguous | 0.5096 | ambiguous | -0.401 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | I |
| P/W | 0.9225 | likely_pathogenic | 0.934 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| P/Y | 0.7575 | likely_pathogenic | 0.7822 | pathogenic | -0.59 | Destabilizing | 1.0 | D | 0.682 | prob.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.