Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23355 | 70288;70289;70290 | chr2:178576069;178576068;178576067 | chr2:179440796;179440795;179440794 |
| N2AB | 21714 | 65365;65366;65367 | chr2:178576069;178576068;178576067 | chr2:179440796;179440795;179440794 |
| N2A | 20787 | 62584;62585;62586 | chr2:178576069;178576068;178576067 | chr2:179440796;179440795;179440794 |
| N2B | 14290 | 43093;43094;43095 | chr2:178576069;178576068;178576067 | chr2:179440796;179440795;179440794 |
| Novex-1 | 14415 | 43468;43469;43470 | chr2:178576069;178576068;178576067 | chr2:179440796;179440795;179440794 |
| Novex-2 | 14482 | 43669;43670;43671 | chr2:178576069;178576068;178576067 | chr2:179440796;179440795;179440794 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs1249051519  |
None | 0.983 | N | 0.537 | 0.536 | None | gnomAD-4.0.0 | 4.10584E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.3975E-06 | 0 | 0 |
| V/I | rs1249051519 |
-0.113 | 0.873 | N | 0.449 | 0.268 | 0.676505548274 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1249051519 |
-0.113 | 0.873 | N | 0.449 | 0.268 | 0.676505548274 | gnomAD-4.0.0 | 6.84306E-07 | None | None | None | None | I | None | 0 | 0 | None | 3.82731E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.773 | N | 0.431 | 0.326 | 0.68224456972 | gnomAD-4.0.0 | 6.84306E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99583E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.32 | likely_benign | 0.3835 | ambiguous | -0.887 | Destabilizing | 0.892 | D | 0.399 | neutral | N | 0.488859562 | None | None | I |
| V/C | 0.8414 | likely_pathogenic | 0.8627 | pathogenic | -0.808 | Destabilizing | 0.999 | D | 0.529 | neutral | None | None | None | None | I |
| V/D | 0.7446 | likely_pathogenic | 0.7948 | pathogenic | -0.608 | Destabilizing | 0.967 | D | 0.631 | neutral | N | 0.501901388 | None | None | I |
| V/E | 0.5644 | likely_pathogenic | 0.6006 | pathogenic | -0.644 | Destabilizing | 0.975 | D | 0.525 | neutral | None | None | None | None | I |
| V/F | 0.3796 | ambiguous | 0.443 | ambiguous | -0.684 | Destabilizing | 0.983 | D | 0.537 | neutral | N | 0.502915346 | None | None | I |
| V/G | 0.5519 | ambiguous | 0.6192 | pathogenic | -1.134 | Destabilizing | 0.967 | D | 0.585 | neutral | N | 0.513764673 | None | None | I |
| V/H | 0.7788 | likely_pathogenic | 0.8228 | pathogenic | -0.586 | Destabilizing | 0.073 | N | 0.428 | neutral | None | None | None | None | I |
| V/I | 0.0827 | likely_benign | 0.0819 | benign | -0.341 | Destabilizing | 0.873 | D | 0.449 | neutral | N | 0.450694451 | None | None | I |
| V/K | 0.7435 | likely_pathogenic | 0.7815 | pathogenic | -0.898 | Destabilizing | 0.975 | D | 0.565 | neutral | None | None | None | None | I |
| V/L | 0.306 | likely_benign | 0.3339 | benign | -0.341 | Destabilizing | 0.773 | D | 0.431 | neutral | N | 0.490633988 | None | None | I |
| V/M | 0.2397 | likely_benign | 0.2546 | benign | -0.43 | Destabilizing | 0.996 | D | 0.512 | neutral | None | None | None | None | I |
| V/N | 0.4836 | ambiguous | 0.5238 | ambiguous | -0.721 | Destabilizing | 0.975 | D | 0.631 | neutral | None | None | None | None | I |
| V/P | 0.8564 | likely_pathogenic | 0.8807 | pathogenic | -0.487 | Destabilizing | 0.996 | D | 0.564 | neutral | None | None | None | None | I |
| V/Q | 0.5526 | ambiguous | 0.587 | pathogenic | -0.875 | Destabilizing | 0.975 | D | 0.579 | neutral | None | None | None | None | I |
| V/R | 0.6947 | likely_pathogenic | 0.7481 | pathogenic | -0.388 | Destabilizing | 0.975 | D | 0.627 | neutral | None | None | None | None | I |
| V/S | 0.3657 | ambiguous | 0.4337 | ambiguous | -1.171 | Destabilizing | 0.975 | D | 0.525 | neutral | None | None | None | None | I |
| V/T | 0.1877 | likely_benign | 0.2042 | benign | -1.096 | Destabilizing | 0.957 | D | 0.452 | neutral | None | None | None | None | I |
| V/W | 0.9363 | likely_pathogenic | 0.9571 | pathogenic | -0.834 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | I |
| V/Y | 0.7804 | likely_pathogenic | 0.8333 | pathogenic | -0.542 | Destabilizing | 0.95 | D | 0.55 | 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.