Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19622 | 59089;59090;59091 | chr2:178593344;178593343;178593342 | chr2:179458071;179458070;179458069 |
| N2AB | 17981 | 54166;54167;54168 | chr2:178593344;178593343;178593342 | chr2:179458071;179458070;179458069 |
| N2A | 17054 | 51385;51386;51387 | chr2:178593344;178593343;178593342 | chr2:179458071;179458070;179458069 |
| N2B | 10557 | 31894;31895;31896 | chr2:178593344;178593343;178593342 | chr2:179458071;179458070;179458069 |
| Novex-1 | 10682 | 32269;32270;32271 | chr2:178593344;178593343;178593342 | chr2:179458071;179458070;179458069 |
| Novex-2 | 10749 | 32470;32471;32472 | chr2:178593344;178593343;178593342 | chr2:179458071;179458070;179458069 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | None | None | 0.896 | N | 0.364 | 0.519 | 0.612105117874 | gnomAD-4.0.0 | 6.84368E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15964E-05 | 0 |
| S/Y | rs144576333  |
-0.761 | 0.963 | N | 0.35 | 0.455 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/Y | rs144576333 |
-0.761 | 0.963 | N | 0.35 | 0.455 | None | gnomAD-4.0.0 | 6.84368E-07 | None | None | None | None | N | None | 2.99007E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1163 | likely_benign | 0.1063 | benign | -0.525 | Destabilizing | 0.001 | N | 0.085 | neutral | N | 0.483099579 | None | None | N |
| S/C | 0.2492 | likely_benign | 0.2289 | benign | -0.367 | Destabilizing | 0.99 | D | 0.259 | neutral | N | 0.517215761 | None | None | N |
| S/D | 0.8227 | likely_pathogenic | 0.8205 | pathogenic | 0.066 | Stabilizing | 0.617 | D | 0.303 | neutral | None | None | None | None | N |
| S/E | 0.8436 | likely_pathogenic | 0.8485 | pathogenic | -0.009 | Destabilizing | 0.617 | D | 0.243 | neutral | None | None | None | None | N |
| S/F | 0.6421 | likely_pathogenic | 0.6287 | pathogenic | -0.914 | Destabilizing | 0.896 | D | 0.364 | neutral | N | 0.492932988 | None | None | N |
| S/G | 0.1264 | likely_benign | 0.1134 | benign | -0.684 | Destabilizing | 0.25 | N | 0.315 | neutral | None | None | None | None | N |
| S/H | 0.7213 | likely_pathogenic | 0.7312 | pathogenic | -1.131 | Destabilizing | 0.992 | D | 0.257 | neutral | None | None | None | None | N |
| S/I | 0.6637 | likely_pathogenic | 0.6613 | pathogenic | -0.231 | Destabilizing | 0.739 | D | 0.379 | neutral | None | None | None | None | N |
| S/K | 0.9475 | likely_pathogenic | 0.949 | pathogenic | -0.679 | Destabilizing | 0.617 | D | 0.241 | neutral | None | None | None | None | N |
| S/L | 0.2858 | likely_benign | 0.2662 | benign | -0.231 | Destabilizing | 0.447 | N | 0.255 | neutral | None | None | None | None | N |
| S/M | 0.4309 | ambiguous | 0.4301 | ambiguous | 0.039 | Stabilizing | 0.92 | D | 0.26 | neutral | None | None | None | None | N |
| S/N | 0.4096 | ambiguous | 0.3958 | ambiguous | -0.377 | Destabilizing | 0.617 | D | 0.375 | neutral | None | None | None | None | N |
| S/P | 0.9236 | likely_pathogenic | 0.9069 | pathogenic | -0.298 | Destabilizing | 0.896 | D | 0.299 | neutral | N | 0.495059355 | None | None | N |
| S/Q | 0.7754 | likely_pathogenic | 0.782 | pathogenic | -0.627 | Destabilizing | 0.92 | D | 0.299 | neutral | None | None | None | None | N |
| S/R | 0.9294 | likely_pathogenic | 0.9316 | pathogenic | -0.441 | Destabilizing | 0.85 | D | 0.307 | neutral | None | None | None | None | N |
| S/T | 0.1736 | likely_benign | 0.1763 | benign | -0.499 | Destabilizing | 0.004 | N | 0.125 | neutral | N | 0.51913495 | None | None | N |
| S/V | 0.5334 | ambiguous | 0.5251 | ambiguous | -0.298 | Destabilizing | 0.447 | N | 0.248 | neutral | None | None | None | None | N |
| S/W | 0.7223 | likely_pathogenic | 0.7179 | pathogenic | -0.876 | Destabilizing | 0.992 | D | 0.491 | neutral | None | None | None | None | N |
| S/Y | 0.5761 | likely_pathogenic | 0.5632 | ambiguous | -0.638 | Destabilizing | 0.963 | D | 0.35 | neutral | N | 0.512353916 | 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.