Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1716 | 5371;5372;5373 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
| N2AB | 1716 | 5371;5372;5373 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
| N2A | 1716 | 5371;5372;5373 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
| N2B | 1670 | 5233;5234;5235 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
| Novex-1 | 1670 | 5233;5234;5235 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
| Novex-2 | 1670 | 5233;5234;5235 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
| Novex-3 | 1716 | 5371;5372;5373 | chr2:178776718;178776717;178776716 | chr2:179641445;179641444;179641443 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs779424493  |
-0.998 | 0.019 | N | 0.489 | 0.316 | 0.477994580393 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | I | None | 1.23077E-04 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 8.84E-06 | 0 |
| R/C | rs779424493 |
-0.998 | 0.019 | N | 0.489 | 0.316 | 0.477994580393 | 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 |
| R/C | rs779424493 |
-0.998 | 0.019 | N | 0.489 | 0.316 | 0.477994580393 | gnomAD-4.0.0 | 6.81556E-06 | None | None | None | None | I | None | 2.66994E-05 | 1.66706E-05 | None | 0 | 0 | None | 0 | 0 | 5.08464E-06 | 0 | 3.20123E-05 |
| R/H | rs771659260 |
-1.523 | 0.95 | N | 0.312 | 0.29 | 0.324161360171 | gnomAD-2.1.1 | 4.39E-05 | None | None | None | None | I | None | 0 | 1.44802E-04 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 4.42E-05 | 0 |
| R/H | rs771659260 |
-1.523 | 0.95 | N | 0.312 | 0.29 | 0.324161360171 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 1.30907E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 4.78469E-04 |
| R/H | rs771659260 |
-1.523 | 0.95 | N | 0.312 | 0.29 | 0.324161360171 | gnomAD-4.0.0 | 2.47839E-05 | None | None | None | None | I | None | 0 | 1.16698E-04 | None | 0 | 6.68807E-05 | None | 1.56187E-05 | 1.6442E-04 | 1.94913E-05 | 1.09789E-05 | 6.40225E-05 |
| R/P | None | None | 0.896 | N | 0.44 | 0.349 | 0.471292358255 | gnomAD-4.0.0 | 6.84107E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5563 | ambiguous | 0.5079 | ambiguous | 0.078 | Stabilizing | 0.116 | N | 0.417 | neutral | None | None | None | None | I |
| R/C | 0.3657 | ambiguous | 0.2929 | benign | -0.283 | Destabilizing | 0.019 | N | 0.489 | neutral | N | 0.512243175 | None | None | I |
| R/D | 0.7733 | likely_pathogenic | 0.7317 | pathogenic | -0.242 | Destabilizing | 0.69 | D | 0.407 | neutral | None | None | None | None | I |
| R/E | 0.5084 | ambiguous | 0.4677 | ambiguous | -0.161 | Destabilizing | 0.241 | N | 0.397 | neutral | None | None | None | None | I |
| R/F | 0.8012 | likely_pathogenic | 0.7473 | pathogenic | -0.158 | Destabilizing | 0.818 | D | 0.446 | neutral | None | None | None | None | I |
| R/G | 0.3966 | ambiguous | 0.3654 | ambiguous | -0.109 | Destabilizing | 0.549 | D | 0.464 | neutral | N | 0.487518738 | None | None | I |
| R/H | 0.1681 | likely_benign | 0.1776 | benign | -0.728 | Destabilizing | 0.95 | D | 0.312 | neutral | N | 0.511230186 | None | None | I |
| R/I | 0.5387 | ambiguous | 0.479 | ambiguous | 0.534 | Stabilizing | 0.69 | D | 0.462 | neutral | None | None | None | None | I |
| R/K | 0.1836 | likely_benign | 0.1606 | benign | -0.067 | Destabilizing | 0.116 | N | 0.445 | neutral | None | None | None | None | I |
| R/L | 0.4149 | ambiguous | 0.3866 | ambiguous | 0.534 | Stabilizing | 0.378 | N | 0.456 | neutral | N | 0.461896286 | None | None | I |
| R/M | 0.6057 | likely_pathogenic | 0.5505 | ambiguous | -0.106 | Destabilizing | 0.818 | D | 0.35 | neutral | None | None | None | None | I |
| R/N | 0.6381 | likely_pathogenic | 0.5677 | pathogenic | -0.094 | Destabilizing | 0.69 | D | 0.355 | neutral | None | None | None | None | I |
| R/P | 0.6605 | likely_pathogenic | 0.666 | pathogenic | 0.402 | Stabilizing | 0.896 | D | 0.44 | neutral | N | 0.477678647 | None | None | I |
| R/Q | 0.1444 | likely_benign | 0.1335 | benign | -0.065 | Destabilizing | 0.008 | N | 0.273 | neutral | None | None | None | None | I |
| R/S | 0.5911 | likely_pathogenic | 0.5438 | ambiguous | -0.283 | Destabilizing | 0.549 | D | 0.41 | neutral | N | 0.453532463 | None | None | I |
| R/T | 0.4426 | ambiguous | 0.3919 | ambiguous | -0.067 | Destabilizing | 0.388 | N | 0.427 | neutral | None | None | None | None | I |
| R/V | 0.5572 | ambiguous | 0.5003 | ambiguous | 0.402 | Stabilizing | 0.527 | D | 0.428 | neutral | None | None | None | None | I |
| R/W | 0.4082 | ambiguous | 0.395 | ambiguous | -0.323 | Destabilizing | 0.981 | D | 0.584 | neutral | None | None | None | None | I |
| R/Y | 0.5627 | ambiguous | 0.5084 | ambiguous | 0.098 | Stabilizing | 0.932 | D | 0.427 | 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.