Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26321 | 79186;79187;79188 | chr2:178567171;178567170;178567169 | chr2:179431898;179431897;179431896 |
| N2AB | 24680 | 74263;74264;74265 | chr2:178567171;178567170;178567169 | chr2:179431898;179431897;179431896 |
| N2A | 23753 | 71482;71483;71484 | chr2:178567171;178567170;178567169 | chr2:179431898;179431897;179431896 |
| N2B | 17256 | 51991;51992;51993 | chr2:178567171;178567170;178567169 | chr2:179431898;179431897;179431896 |
| Novex-1 | 17381 | 52366;52367;52368 | chr2:178567171;178567170;178567169 | chr2:179431898;179431897;179431896 |
| Novex-2 | 17448 | 52567;52568;52569 | chr2:178567171;178567170;178567169 | chr2:179431898;179431897;179431896 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/Q | rs769466262  |
-0.474 | 0.942 | N | 0.491 | 0.31 | 0.264081493735 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| H/Q | rs769466262 |
-0.474 | 0.942 | N | 0.491 | 0.31 | 0.264081493735 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/Q | rs769466262 |
-0.474 | 0.942 | N | 0.491 | 0.31 | 0.264081493735 | gnomAD-4.0.0 | 8.9724E-06 | None | None | None | None | N | None | 1.69262E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43672E-05 | 0 | 0 |
| H/Y | rs1466788424 |
None | 0.058 | N | 0.244 | 0.26 | 0.225215365344 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/Y | rs1466788424 |
None | 0.058 | N | 0.244 | 0.26 | 0.225215365344 | gnomAD-4.0.0 | 6.57462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47042E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.6556 | likely_pathogenic | 0.6076 | pathogenic | -1.291 | Destabilizing | 0.86 | D | 0.591 | neutral | None | None | None | None | N |
| H/C | 0.2099 | likely_benign | 0.201 | benign | -0.535 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| H/D | 0.7309 | likely_pathogenic | 0.6276 | pathogenic | -0.769 | Destabilizing | 0.698 | D | 0.544 | neutral | N | 0.468455496 | None | None | N |
| H/E | 0.8228 | likely_pathogenic | 0.7822 | pathogenic | -0.632 | Destabilizing | 0.86 | D | 0.445 | neutral | None | None | None | None | N |
| H/F | 0.392 | ambiguous | 0.3981 | ambiguous | 0.152 | Stabilizing | 0.915 | D | 0.588 | neutral | None | None | None | None | N |
| H/G | 0.5101 | ambiguous | 0.4071 | ambiguous | -1.671 | Destabilizing | 0.754 | D | 0.588 | neutral | None | None | None | None | N |
| H/I | 0.8834 | likely_pathogenic | 0.8845 | pathogenic | -0.212 | Destabilizing | 0.978 | D | 0.686 | prob.neutral | None | None | None | None | N |
| H/K | 0.7459 | likely_pathogenic | 0.7171 | pathogenic | -0.954 | Destabilizing | 0.86 | D | 0.555 | neutral | None | None | None | None | N |
| H/L | 0.4947 | ambiguous | 0.4794 | ambiguous | -0.212 | Destabilizing | 0.822 | D | 0.667 | neutral | N | 0.478356997 | None | None | N |
| H/M | 0.8347 | likely_pathogenic | 0.8279 | pathogenic | -0.405 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| H/N | 0.2146 | likely_benign | 0.1734 | benign | -1.17 | Destabilizing | 0.014 | N | 0.327 | neutral | N | 0.451947165 | None | None | N |
| H/P | 0.9731 | likely_pathogenic | 0.9651 | pathogenic | -0.555 | Destabilizing | 0.99 | D | 0.659 | neutral | N | 0.510793299 | None | None | N |
| H/Q | 0.5537 | ambiguous | 0.5181 | ambiguous | -0.865 | Destabilizing | 0.942 | D | 0.491 | neutral | N | 0.470190242 | None | None | N |
| H/R | 0.3782 | ambiguous | 0.3597 | ambiguous | -1.226 | Destabilizing | 0.942 | D | 0.485 | neutral | N | 0.491273558 | None | None | N |
| H/S | 0.3787 | ambiguous | 0.313 | benign | -1.345 | Destabilizing | 0.754 | D | 0.511 | neutral | None | None | None | None | N |
| H/T | 0.6806 | likely_pathogenic | 0.6463 | pathogenic | -1.103 | Destabilizing | 0.86 | D | 0.634 | neutral | None | None | None | None | N |
| H/V | 0.8016 | likely_pathogenic | 0.8058 | pathogenic | -0.555 | Destabilizing | 0.956 | D | 0.654 | neutral | None | None | None | None | N |
| H/W | 0.5743 | likely_pathogenic | 0.5851 | pathogenic | 0.592 | Stabilizing | 0.994 | D | 0.662 | neutral | None | None | None | None | N |
| H/Y | 0.1286 | likely_benign | 0.1306 | benign | 0.607 | Stabilizing | 0.058 | N | 0.244 | neutral | N | 0.461068081 | 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.