Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14741 | 44446;44447;44448 | chr2:178630301;178630300;178630299 | chr2:179495028;179495027;179495026 |
| N2AB | 13100 | 39523;39524;39525 | chr2:178630301;178630300;178630299 | chr2:179495028;179495027;179495026 |
| N2A | 12173 | 36742;36743;36744 | chr2:178630301;178630300;178630299 | chr2:179495028;179495027;179495026 |
| N2B | 5676 | 17251;17252;17253 | chr2:178630301;178630300;178630299 | chr2:179495028;179495027;179495026 |
| Novex-1 | 5801 | 17626;17627;17628 | chr2:178630301;178630300;178630299 | chr2:179495028;179495027;179495026 |
| Novex-2 | 5868 | 17827;17828;17829 | chr2:178630301;178630300;178630299 | chr2:179495028;179495027;179495026 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs745305661  |
-0.867 | None | N | 0.143 | 0.045 | 0.0611884634855 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs745305661 |
-0.867 | None | N | 0.143 | 0.045 | 0.0611884634855 | gnomAD-4.0.0 | 1.59272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78272E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/M | rs778576436 |
0.077 | 0.996 | N | 0.485 | 0.314 | 0.285698343383 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 1.78E-05 | 0 |
| T/M | rs778576436 |
0.077 | 0.996 | N | 0.485 | 0.314 | 0.285698343383 | gnomAD-4.0.0 | 2.0535E-05 | None | None | None | None | N | None | 1.79501E-04 | 2.23754E-05 | None | 0 | 0 | None | 0 | 0 | 1.52954E-05 | 4.63919E-05 | 3.31488E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0732 | likely_benign | 0.0734 | benign | -0.784 | Destabilizing | None | N | 0.143 | neutral | N | 0.371570848 | None | None | N |
| T/C | 0.622 | likely_pathogenic | 0.5767 | pathogenic | -0.42 | Destabilizing | 0.953 | D | 0.483 | neutral | None | None | None | None | N |
| T/D | 0.5656 | likely_pathogenic | 0.6645 | pathogenic | -0.54 | Destabilizing | 0.842 | D | 0.493 | neutral | None | None | None | None | N |
| T/E | 0.4303 | ambiguous | 0.4647 | ambiguous | -0.497 | Destabilizing | 0.428 | N | 0.485 | neutral | None | None | None | None | N |
| T/F | 0.5589 | ambiguous | 0.5459 | ambiguous | -0.631 | Destabilizing | 0.842 | D | 0.624 | neutral | None | None | None | None | N |
| T/G | 0.2728 | likely_benign | 0.2909 | benign | -1.103 | Destabilizing | 0.134 | N | 0.531 | neutral | None | None | None | None | N |
| T/H | 0.4975 | ambiguous | 0.5079 | ambiguous | -1.404 | Destabilizing | 0.984 | D | 0.614 | neutral | None | None | None | None | N |
| T/I | 0.4154 | ambiguous | 0.3997 | ambiguous | -0.009 | Destabilizing | 0.428 | N | 0.497 | neutral | None | None | None | None | N |
| T/K | 0.3818 | ambiguous | 0.4121 | ambiguous | -0.928 | Destabilizing | 0.589 | D | 0.485 | neutral | N | 0.42176576 | None | None | N |
| T/L | 0.2194 | likely_benign | 0.2115 | benign | -0.009 | Destabilizing | 0.272 | N | 0.545 | neutral | None | None | None | None | N |
| T/M | 0.123 | likely_benign | 0.1155 | benign | 0.257 | Stabilizing | 0.996 | D | 0.485 | neutral | N | 0.431399446 | None | None | N |
| T/N | 0.1985 | likely_benign | 0.2249 | benign | -0.957 | Destabilizing | 0.842 | D | 0.435 | neutral | None | None | None | None | N |
| T/P | 0.3368 | likely_benign | 0.4238 | ambiguous | -0.233 | Destabilizing | 0.8 | D | 0.478 | neutral | N | 0.463598821 | None | None | N |
| T/Q | 0.357 | ambiguous | 0.3434 | ambiguous | -0.998 | Destabilizing | 0.842 | D | 0.481 | neutral | None | None | None | None | N |
| T/R | 0.304 | likely_benign | 0.3461 | ambiguous | -0.791 | Destabilizing | 0.834 | D | 0.482 | neutral | N | 0.421490435 | None | None | N |
| T/S | 0.1325 | likely_benign | 0.1409 | benign | -1.18 | Destabilizing | 0.104 | N | 0.493 | neutral | N | 0.412260958 | None | None | N |
| T/V | 0.2799 | likely_benign | 0.2631 | benign | -0.233 | Destabilizing | 0.134 | N | 0.453 | neutral | None | None | None | None | N |
| T/W | 0.8319 | likely_pathogenic | 0.8537 | pathogenic | -0.657 | Destabilizing | 0.984 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/Y | 0.5426 | ambiguous | 0.5509 | ambiguous | -0.425 | Destabilizing | 0.942 | D | 0.625 | 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.