Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20060 | 60403;60404;60405 | chr2:178591641;178591640;178591639 | chr2:179456368;179456367;179456366 |
| N2AB | 18419 | 55480;55481;55482 | chr2:178591641;178591640;178591639 | chr2:179456368;179456367;179456366 |
| N2A | 17492 | 52699;52700;52701 | chr2:178591641;178591640;178591639 | chr2:179456368;179456367;179456366 |
| N2B | 10995 | 33208;33209;33210 | chr2:178591641;178591640;178591639 | chr2:179456368;179456367;179456366 |
| Novex-1 | 11120 | 33583;33584;33585 | chr2:178591641;178591640;178591639 | chr2:179456368;179456367;179456366 |
| Novex-2 | 11187 | 33784;33785;33786 | chr2:178591641;178591640;178591639 | chr2:179456368;179456367;179456366 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/H | rs143364796  |
-0.253 | 0.928 | N | 0.523 | 0.265 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/H | rs143364796 |
-0.253 | 0.928 | N | 0.523 | 0.265 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 5.82524E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/H | rs143364796 |
-0.253 | 0.928 | N | 0.523 | 0.265 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| L/H | rs143364796 |
-0.253 | 0.928 | N | 0.523 | 0.265 | None | gnomAD-4.0.0 | 1.48747E-05 | None | None | None | None | I | None | 0 | 1.66678E-05 | None | 0 | 5.13301E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/I | rs756818819 |
-0.293 | 0.001 | N | 0.209 | 0.1 | 0.281780670237 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| L/I | rs756818819 |
-0.293 | 0.001 | N | 0.209 | 0.1 | 0.281780670237 | gnomAD-4.0.0 | 1.59199E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85981E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2434 | likely_benign | 0.2387 | benign | -0.844 | Destabilizing | 0.207 | N | 0.514 | neutral | None | None | None | None | I |
| L/C | 0.5301 | ambiguous | 0.5787 | pathogenic | -0.717 | Destabilizing | 0.981 | D | 0.535 | neutral | None | None | None | None | I |
| L/D | 0.5064 | ambiguous | 0.5307 | ambiguous | -0.489 | Destabilizing | 0.818 | D | 0.539 | neutral | None | None | None | None | I |
| L/E | 0.2795 | likely_benign | 0.3018 | benign | -0.57 | Destabilizing | 0.69 | D | 0.493 | neutral | None | None | None | None | I |
| L/F | 0.1583 | likely_benign | 0.1574 | benign | -0.735 | Destabilizing | 0.627 | D | 0.516 | neutral | N | 0.471474289 | None | None | I |
| L/G | 0.5121 | ambiguous | 0.5123 | ambiguous | -1.035 | Destabilizing | 0.818 | D | 0.489 | neutral | None | None | None | None | I |
| L/H | 0.2104 | likely_benign | 0.2149 | benign | -0.224 | Destabilizing | 0.928 | D | 0.523 | neutral | N | 0.434476126 | None | None | I |
| L/I | 0.1071 | likely_benign | 0.1065 | benign | -0.451 | Destabilizing | 0.001 | N | 0.209 | neutral | N | 0.514494347 | None | None | I |
| L/K | 0.1731 | likely_benign | 0.1984 | benign | -0.575 | Destabilizing | 0.241 | N | 0.492 | neutral | None | None | None | None | I |
| L/M | 0.1256 | likely_benign | 0.1229 | benign | -0.493 | Destabilizing | 0.69 | D | 0.545 | neutral | None | None | None | None | I |
| L/N | 0.255 | likely_benign | 0.2624 | benign | -0.369 | Destabilizing | 0.69 | D | 0.533 | neutral | None | None | None | None | I |
| L/P | 0.2111 | likely_benign | 0.1982 | benign | -0.549 | Destabilizing | 0.912 | D | 0.54 | neutral | N | 0.362359737 | None | None | I |
| L/Q | 0.1306 | likely_benign | 0.1331 | benign | -0.612 | Destabilizing | 0.69 | D | 0.525 | neutral | None | None | None | None | I |
| L/R | 0.1626 | likely_benign | 0.1731 | benign | 0.057 | Stabilizing | 0.001 | N | 0.233 | neutral | N | 0.382239151 | None | None | I |
| L/S | 0.2677 | likely_benign | 0.2627 | benign | -0.822 | Destabilizing | 0.388 | N | 0.502 | neutral | None | None | None | None | I |
| L/T | 0.2378 | likely_benign | 0.2412 | benign | -0.794 | Destabilizing | 0.388 | N | 0.516 | neutral | None | None | None | None | I |
| L/V | 0.1156 | likely_benign | 0.1098 | benign | -0.549 | Destabilizing | 0.033 | N | 0.543 | neutral | N | 0.428318157 | None | None | I |
| L/W | 0.2585 | likely_benign | 0.2652 | benign | -0.733 | Destabilizing | 0.981 | D | 0.649 | neutral | None | None | None | None | I |
| L/Y | 0.2872 | likely_benign | 0.299 | benign | -0.509 | Destabilizing | 0.818 | D | 0.535 | 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.