Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29593 | 89002;89003;89004 | chr2:178554570;178554569;178554568 | chr2:179419297;179419296;179419295 |
| N2AB | 27952 | 84079;84080;84081 | chr2:178554570;178554569;178554568 | chr2:179419297;179419296;179419295 |
| N2A | 27025 | 81298;81299;81300 | chr2:178554570;178554569;178554568 | chr2:179419297;179419296;179419295 |
| N2B | 20528 | 61807;61808;61809 | chr2:178554570;178554569;178554568 | chr2:179419297;179419296;179419295 |
| Novex-1 | 20653 | 62182;62183;62184 | chr2:178554570;178554569;178554568 | chr2:179419297;179419296;179419295 |
| Novex-2 | 20720 | 62383;62384;62385 | chr2:178554570;178554569;178554568 | chr2:179419297;179419296;179419295 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1412856815  |
-0.091 | None | N | 0.159 | 0.06 | 0.210429274316 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| I/L | rs1412856815 |
-0.091 | None | N | 0.159 | 0.06 | 0.210429274316 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79885E-06 | 0 | 0 |
| I/T | None | None | 0.062 | N | 0.485 | 0.304 | 0.566408210792 | gnomAD-4.0.0 | 3.18212E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85781E-06 | 1.43271E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3527 | ambiguous | 0.3677 | ambiguous | -1.669 | Destabilizing | 0.035 | N | 0.463 | neutral | None | None | None | None | N |
| I/C | 0.5452 | ambiguous | 0.5475 | ambiguous | -1.173 | Destabilizing | 0.824 | D | 0.541 | neutral | None | None | None | None | N |
| I/D | 0.898 | likely_pathogenic | 0.9001 | pathogenic | -0.812 | Destabilizing | 0.555 | D | 0.637 | neutral | None | None | None | None | N |
| I/E | 0.8198 | likely_pathogenic | 0.8066 | pathogenic | -0.672 | Destabilizing | 0.555 | D | 0.621 | neutral | None | None | None | None | N |
| I/F | 0.1813 | likely_benign | 0.1863 | benign | -0.81 | Destabilizing | 0.188 | N | 0.491 | neutral | N | 0.364944256 | None | None | N |
| I/G | 0.7539 | likely_pathogenic | 0.7694 | pathogenic | -2.119 | Highly Destabilizing | 0.555 | D | 0.632 | neutral | None | None | None | None | N |
| I/H | 0.6516 | likely_pathogenic | 0.6453 | pathogenic | -1.246 | Destabilizing | 0.935 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/K | 0.6668 | likely_pathogenic | 0.6428 | pathogenic | -1.112 | Destabilizing | 0.555 | D | 0.633 | neutral | None | None | None | None | N |
| I/L | 0.0982 | likely_benign | 0.1007 | benign | -0.442 | Destabilizing | None | N | 0.159 | neutral | N | 0.386242248 | None | None | N |
| I/M | 0.0977 | likely_benign | 0.1012 | benign | -0.52 | Destabilizing | 0.317 | N | 0.479 | neutral | N | 0.447138778 | None | None | N |
| I/N | 0.5146 | ambiguous | 0.5303 | ambiguous | -1.239 | Destabilizing | 0.741 | D | 0.674 | neutral | N | 0.509958106 | None | None | N |
| I/P | 0.9699 | likely_pathogenic | 0.9731 | pathogenic | -0.823 | Destabilizing | 0.791 | D | 0.641 | neutral | None | None | None | None | N |
| I/Q | 0.6586 | likely_pathogenic | 0.6476 | pathogenic | -1.16 | Destabilizing | 0.791 | D | 0.663 | neutral | None | None | None | None | N |
| I/R | 0.5953 | likely_pathogenic | 0.5872 | pathogenic | -0.812 | Destabilizing | 0.555 | D | 0.672 | neutral | None | None | None | None | N |
| I/S | 0.4125 | ambiguous | 0.4411 | ambiguous | -2.019 | Highly Destabilizing | 0.317 | N | 0.562 | neutral | N | 0.457355772 | None | None | N |
| I/T | 0.2612 | likely_benign | 0.2754 | benign | -1.729 | Destabilizing | 0.062 | N | 0.485 | neutral | N | 0.442116961 | None | None | N |
| I/V | 0.0721 | likely_benign | 0.0738 | benign | -0.823 | Destabilizing | None | N | 0.146 | neutral | N | 0.384353949 | None | None | N |
| I/W | 0.8754 | likely_pathogenic | 0.8743 | pathogenic | -0.976 | Destabilizing | 0.935 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/Y | 0.5711 | likely_pathogenic | 0.5738 | pathogenic | -0.695 | Destabilizing | 0.555 | D | 0.536 | 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.