Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1536 | 4831;4832;4833 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
| N2AB | 1536 | 4831;4832;4833 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
| N2A | 1536 | 4831;4832;4833 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
| N2B | 1490 | 4693;4694;4695 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
| Novex-1 | 1490 | 4693;4694;4695 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
| Novex-2 | 1490 | 4693;4694;4695 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
| Novex-3 | 1536 | 4831;4832;4833 | chr2:178777459;178777458;178777457 | chr2:179642186;179642185;179642184 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs879055295  |
-0.057 | 1.0 | D | 0.637 | 0.448 | 0.401327265625 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/S | rs879055295 |
-0.057 | 1.0 | D | 0.637 | 0.448 | 0.401327265625 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs879055295 |
-0.057 | 1.0 | D | 0.637 | 0.448 | 0.401327265625 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | I | None | 2.41429E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs879055295 |
-0.136 | 1.0 | D | 0.714 | 0.507 | 0.440288351245 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| A/V | None | None | 1.0 | N | 0.675 | 0.422 | 0.47290127212 | gnomAD-4.0.0 | 9.57875E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25913E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.898 | likely_pathogenic | 0.9098 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| A/D | 0.9847 | likely_pathogenic | 0.9873 | pathogenic | -0.476 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| A/E | 0.967 | likely_pathogenic | 0.9712 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.551544821 | None | None | I |
| A/F | 0.6872 | likely_pathogenic | 0.7116 | pathogenic | -0.886 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | I |
| A/G | 0.4866 | ambiguous | 0.5323 | ambiguous | -0.26 | Destabilizing | 1.0 | D | 0.6 | neutral | D | 0.553593769 | None | None | I |
| A/H | 0.9377 | likely_pathogenic | 0.9386 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| A/I | 0.9196 | likely_pathogenic | 0.9363 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| A/K | 0.9869 | likely_pathogenic | 0.9885 | pathogenic | -0.586 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| A/L | 0.7951 | likely_pathogenic | 0.819 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| A/M | 0.8581 | likely_pathogenic | 0.8837 | pathogenic | -0.521 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| A/N | 0.9401 | likely_pathogenic | 0.948 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| A/P | 0.9804 | likely_pathogenic | 0.9842 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.714658378 | None | None | I |
| A/Q | 0.9311 | likely_pathogenic | 0.9365 | pathogenic | -0.565 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| A/R | 0.9514 | likely_pathogenic | 0.9542 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| A/S | 0.3992 | ambiguous | 0.4342 | ambiguous | -0.498 | Destabilizing | 1.0 | D | 0.637 | neutral | D | 0.553040668 | None | None | I |
| A/T | 0.7861 | likely_pathogenic | 0.8234 | pathogenic | -0.572 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | D | 0.589871917 | None | None | I |
| A/V | 0.7368 | likely_pathogenic | 0.7841 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.675 | neutral | N | 0.509820485 | None | None | I |
| A/W | 0.9628 | likely_pathogenic | 0.9641 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| A/Y | 0.8727 | likely_pathogenic | 0.8794 | pathogenic | -0.671 | Destabilizing | 1.0 | D | 0.786 | deleterious | 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.