Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
| N2AB | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
| N2A | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
| N2B | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
| Novex-1 | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
| Novex-2 | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
| Novex-3 | 42 | 349;350;351 | chr2:178802309;178802308;178802307 | chr2:179667036;179667035;179667034 |
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/E | None | None | 0.996 | N | 0.418 | 0.476 | 0.478451964739 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | -0.33(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/G | rs200838218  |
-0.28 | 1.0 | N | 0.694 | 0.681 | 0.463758542814 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | -0.297(TCAP) | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs200838218 |
-0.28 | 1.0 | N | 0.694 | 0.681 | 0.463758542814 | gnomAD-4.0.0 | 2.05223E-06 | None | None | None | -0.297(TCAP) | N | None | 5.97372E-05 | 0 | None | 0 | 0 | None | 0 | 1.73491E-04 | 0 | 0 | 0 |
| D/N | rs759317260 |
0.291 | 1.0 | N | 0.629 | 0.429 | 0.389126455913 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | -1.374(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/N | rs759317260 |
0.291 | 1.0 | N | 0.629 | 0.429 | 0.389126455913 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.374(TCAP) | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs759317260 |
0.291 | 1.0 | N | 0.629 | 0.429 | 0.389126455913 | gnomAD-4.0.0 | 1.85874E-06 | None | None | None | -1.374(TCAP) | N | None | 1.33469E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.19573E-05 | 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 | 0.5773 | likely_pathogenic | 0.6276 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | D | 0.552520686 | None | -0.116(TCAP) | N |
| D/C | 0.9648 | likely_pathogenic | 0.9715 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | -0.239(TCAP) | N |
| D/E | 0.4364 | ambiguous | 0.473 | ambiguous | -0.387 | Destabilizing | 0.996 | D | 0.418 | neutral | N | 0.50693466 | None | -0.33(TCAP) | N |
| D/F | 0.9434 | likely_pathogenic | 0.9566 | pathogenic | -0.207 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | -0.02(TCAP) | N |
| D/G | 0.3474 | ambiguous | 0.4098 | ambiguous | -0.794 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.509510728 | None | -0.297(TCAP) | N |
| D/H | 0.7913 | likely_pathogenic | 0.843 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.607 | neutral | D | 0.643140133 | None | 0.801(TCAP) | N |
| D/I | 0.9405 | likely_pathogenic | 0.9528 | pathogenic | 0.149 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | 0.39(TCAP) | N |
| D/K | 0.8636 | likely_pathogenic | 0.8985 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | 0.222(TCAP) | N |
| D/L | 0.8729 | likely_pathogenic | 0.8934 | pathogenic | 0.149 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | 0.39(TCAP) | N |
| D/M | 0.9613 | likely_pathogenic | 0.9688 | pathogenic | 0.395 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | 1.007(TCAP) | N |
| D/N | 0.1841 | likely_benign | 0.2211 | benign | -0.431 | Destabilizing | 1.0 | D | 0.629 | neutral | N | 0.447422438 | None | -1.374(TCAP) | N |
| D/P | 0.9902 | likely_pathogenic | 0.9911 | pathogenic | -0.054 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | 0.23(TCAP) | N |
| D/Q | 0.7688 | likely_pathogenic | 0.8168 | pathogenic | -0.346 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | -0.789(TCAP) | N |
| D/R | 0.8414 | likely_pathogenic | 0.8791 | pathogenic | 0.193 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | 0.162(TCAP) | N |
| D/S | 0.3415 | ambiguous | 0.4013 | ambiguous | -0.586 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | -1.127(TCAP) | N |
| D/T | 0.8281 | likely_pathogenic | 0.8557 | pathogenic | -0.37 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | -0.929(TCAP) | N |
| D/V | 0.8303 | likely_pathogenic | 0.8572 | pathogenic | -0.054 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.665784791 | None | 0.23(TCAP) | N |
| D/W | 0.9857 | likely_pathogenic | 0.9892 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | -0.217(TCAP) | N |
| D/Y | 0.6729 | likely_pathogenic | 0.7255 | pathogenic | 0.04 | Stabilizing | 1.0 | D | 0.652 | neutral | D | 0.736809657 | None | -0.024(TCAP) | 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.