Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3986 | 12181;12182;12183 | chr2:178741277;178741276;178741275 | chr2:179606004;179606003;179606002 |
| N2AB | 3669 | 11230;11231;11232 | chr2:178741277;178741276;178741275 | chr2:179606004;179606003;179606002 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3623 | 11092;11093;11094 | chr2:178741277;178741276;178741275 | chr2:179606004;179606003;179606002 |
| Novex-1 | 3748 | 11467;11468;11469 | chr2:178741277;178741276;178741275 | chr2:179606004;179606003;179606002 |
| Novex-2 | 3815 | 11668;11669;11670 | chr2:178741277;178741276;178741275 | chr2:179606004;179606003;179606002 |
| 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/S | rs760585458  |
-2.185 | 0.549 | D | 0.569 | 0.501 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/S | rs760585458 |
-2.185 | 0.549 | D | 0.569 | 0.501 | None | gnomAD-4.0.0 | 2.05257E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69829E-06 | 0 | 0 |
| I/V | rs763816587 |
-0.857 | 0.002 | N | 0.091 | 0.062 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs763816587 |
-0.857 | 0.002 | N | 0.091 | 0.062 | None | 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 |
| I/V | rs763816587 |
-0.857 | 0.002 | N | 0.091 | 0.062 | None | gnomAD-4.0.0 | 6.56996E-06 | None | None | None | None | I | None | 2.41208E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.541 | ambiguous | 0.507 | ambiguous | -2.126 | Highly Destabilizing | 0.25 | N | 0.421 | neutral | None | None | None | None | I |
| I/C | 0.798 | likely_pathogenic | 0.7801 | pathogenic | -1.395 | Destabilizing | 0.977 | D | 0.552 | neutral | None | None | None | None | I |
| I/D | 0.9017 | likely_pathogenic | 0.8714 | pathogenic | -1.776 | Destabilizing | 0.972 | D | 0.643 | neutral | None | None | None | None | I |
| I/E | 0.8015 | likely_pathogenic | 0.7604 | pathogenic | -1.62 | Destabilizing | 0.92 | D | 0.645 | neutral | None | None | None | None | I |
| I/F | 0.2615 | likely_benign | 0.2598 | benign | -1.253 | Destabilizing | 0.004 | N | 0.254 | neutral | N | 0.516937466 | None | None | I |
| I/G | 0.8633 | likely_pathogenic | 0.8264 | pathogenic | -2.611 | Highly Destabilizing | 0.92 | D | 0.635 | neutral | None | None | None | None | I |
| I/H | 0.7698 | likely_pathogenic | 0.7476 | pathogenic | -1.851 | Destabilizing | 0.992 | D | 0.64 | neutral | None | None | None | None | I |
| I/K | 0.6467 | likely_pathogenic | 0.6095 | pathogenic | -1.54 | Destabilizing | 0.92 | D | 0.644 | neutral | None | None | None | None | I |
| I/L | 0.1538 | likely_benign | 0.164 | benign | -0.777 | Destabilizing | 0.002 | N | 0.101 | neutral | N | 0.505880353 | None | None | I |
| I/M | 0.1254 | likely_benign | 0.128 | benign | -0.675 | Destabilizing | 0.81 | D | 0.509 | neutral | N | 0.507406558 | None | None | I |
| I/N | 0.5525 | ambiguous | 0.5078 | ambiguous | -1.666 | Destabilizing | 0.963 | D | 0.655 | neutral | D | 0.655809071 | None | None | I |
| I/P | 0.9462 | likely_pathogenic | 0.9242 | pathogenic | -1.201 | Destabilizing | 0.972 | D | 0.644 | neutral | None | None | None | None | I |
| I/Q | 0.7088 | likely_pathogenic | 0.6766 | pathogenic | -1.623 | Destabilizing | 0.972 | D | 0.647 | neutral | None | None | None | None | I |
| I/R | 0.5504 | ambiguous | 0.5055 | ambiguous | -1.164 | Destabilizing | 0.92 | D | 0.652 | neutral | None | None | None | None | I |
| I/S | 0.5672 | likely_pathogenic | 0.5246 | ambiguous | -2.404 | Highly Destabilizing | 0.549 | D | 0.569 | neutral | D | 0.573662045 | None | None | I |
| I/T | 0.4155 | ambiguous | 0.3926 | ambiguous | -2.1 | Highly Destabilizing | 0.549 | D | 0.496 | neutral | D | 0.556207529 | None | None | I |
| I/V | 0.0725 | likely_benign | 0.0709 | benign | -1.201 | Destabilizing | 0.002 | N | 0.091 | neutral | N | 0.502413536 | None | None | I |
| I/W | 0.8972 | likely_pathogenic | 0.8863 | pathogenic | -1.491 | Destabilizing | 0.992 | D | 0.657 | neutral | None | None | None | None | I |
| I/Y | 0.6873 | likely_pathogenic | 0.6717 | pathogenic | -1.207 | Destabilizing | 0.739 | D | 0.557 | neutral | 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.