Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24708 | 74347;74348;74349 | chr2:178572010;178572009;178572008 | chr2:179436737;179436736;179436735 |
| N2AB | 23067 | 69424;69425;69426 | chr2:178572010;178572009;178572008 | chr2:179436737;179436736;179436735 |
| N2A | 22140 | 66643;66644;66645 | chr2:178572010;178572009;178572008 | chr2:179436737;179436736;179436735 |
| N2B | 15643 | 47152;47153;47154 | chr2:178572010;178572009;178572008 | chr2:179436737;179436736;179436735 |
| Novex-1 | 15768 | 47527;47528;47529 | chr2:178572010;178572009;178572008 | chr2:179436737;179436736;179436735 |
| Novex-2 | 15835 | 47728;47729;47730 | chr2:178572010;178572009;178572008 | chr2:179436737;179436736;179436735 |
| 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/F | rs1364240717  |
-0.76 | 0.54 | N | 0.409 | 0.082 | 0.450733807028 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/F | rs1364240717 |
-0.76 | 0.54 | N | 0.409 | 0.082 | 0.450733807028 | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41779E-04 | 0 | 0 | 0 |
| I/M | rs758928659 |
-0.45 | 0.473 | N | 0.483 | 0.076 | 0.31411915649 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/M | rs758928659 |
-0.45 | 0.473 | N | 0.483 | 0.076 | 0.31411915649 | gnomAD-4.0.0 | 6.84455E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99622E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2743 | likely_benign | 0.3073 | benign | -1.199 | Destabilizing | 0.187 | N | 0.431 | neutral | None | None | None | None | N |
| I/C | 0.7404 | likely_pathogenic | 0.7789 | pathogenic | -0.81 | Destabilizing | 0.968 | D | 0.413 | neutral | None | None | None | None | N |
| I/D | 0.8176 | likely_pathogenic | 0.8578 | pathogenic | -0.575 | Destabilizing | 0.96 | D | 0.591 | neutral | None | None | None | None | N |
| I/E | 0.5924 | likely_pathogenic | 0.6391 | pathogenic | -0.608 | Destabilizing | 0.854 | D | 0.52 | neutral | None | None | None | None | N |
| I/F | 0.2111 | likely_benign | 0.2301 | benign | -0.833 | Destabilizing | 0.54 | D | 0.409 | neutral | N | 0.503181275 | None | None | N |
| I/G | 0.7423 | likely_pathogenic | 0.7849 | pathogenic | -1.464 | Destabilizing | 0.888 | D | 0.481 | neutral | None | None | None | None | N |
| I/H | 0.5681 | likely_pathogenic | 0.6107 | pathogenic | -0.604 | Destabilizing | 0.974 | D | 0.598 | neutral | None | None | None | None | N |
| I/K | 0.3935 | ambiguous | 0.4386 | ambiguous | -0.813 | Destabilizing | 0.189 | N | 0.535 | neutral | None | None | None | None | N |
| I/L | 0.1191 | likely_benign | 0.135 | benign | -0.579 | Destabilizing | 0.002 | N | 0.287 | neutral | N | 0.479880341 | None | None | N |
| I/M | 0.1015 | likely_benign | 0.1057 | benign | -0.522 | Destabilizing | 0.473 | N | 0.483 | neutral | N | 0.463109443 | None | None | N |
| I/N | 0.3695 | ambiguous | 0.4242 | ambiguous | -0.649 | Destabilizing | 0.948 | D | 0.569 | neutral | N | 0.478593579 | None | None | N |
| I/P | 0.7935 | likely_pathogenic | 0.8464 | pathogenic | -0.753 | Destabilizing | 0.96 | D | 0.603 | neutral | None | None | None | None | N |
| I/Q | 0.4255 | ambiguous | 0.4515 | ambiguous | -0.84 | Destabilizing | 0.909 | D | 0.581 | neutral | None | None | None | None | N |
| I/R | 0.3175 | likely_benign | 0.3623 | ambiguous | -0.199 | Destabilizing | 0.759 | D | 0.571 | neutral | None | None | None | None | N |
| I/S | 0.3036 | likely_benign | 0.3534 | ambiguous | -1.204 | Destabilizing | 0.747 | D | 0.459 | neutral | N | 0.519612165 | None | None | N |
| I/T | 0.1047 | likely_benign | 0.1124 | benign | -1.123 | Destabilizing | 0.202 | N | 0.38 | neutral | N | 0.416089861 | None | None | N |
| I/V | 0.0606 | likely_benign | 0.0616 | benign | -0.753 | Destabilizing | None | N | 0.104 | neutral | N | 0.412001911 | None | None | N |
| I/W | 0.8401 | likely_pathogenic | 0.8594 | pathogenic | -0.865 | Destabilizing | 0.993 | D | 0.661 | prob.neutral | None | None | None | None | N |
| I/Y | 0.606 | likely_pathogenic | 0.6558 | pathogenic | -0.646 | Destabilizing | 0.27 | N | 0.487 | 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.