Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28768 | 86527;86528;86529 | chr2:178559830;178559829;178559828 | chr2:179424557;179424556;179424555 |
| N2AB | 27127 | 81604;81605;81606 | chr2:178559830;178559829;178559828 | chr2:179424557;179424556;179424555 |
| N2A | 26200 | 78823;78824;78825 | chr2:178559830;178559829;178559828 | chr2:179424557;179424556;179424555 |
| N2B | 19703 | 59332;59333;59334 | chr2:178559830;178559829;178559828 | chr2:179424557;179424556;179424555 |
| Novex-1 | 19828 | 59707;59708;59709 | chr2:178559830;178559829;178559828 | chr2:179424557;179424556;179424555 |
| Novex-2 | 19895 | 59908;59909;59910 | chr2:178559830;178559829;178559828 | chr2:179424557;179424556;179424555 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.011 | N | 0.328 | 0.26 | 0.401042353794 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| A/P | None | None | 0.984 | N | 0.457 | 0.252 | 0.241078983079 | gnomAD-4.0.0 | 6.85651E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99594E-07 | 0 | 0 |
| A/S | rs768347250  |
None | 0.103 | N | 0.281 | 0.117 | 0.141422826196 | gnomAD-4.0.0 | 1.3713E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79919E-06 | 0 | 0 |
| A/T | rs768347250 |
None | 0.811 | N | 0.441 | 0.231 | 0.213573922156 | gnomAD-4.0.0 | 1.3713E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79919E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.614 | likely_pathogenic | 0.6141 | pathogenic | -0.712 | Destabilizing | 0.999 | D | 0.427 | neutral | None | None | None | None | N |
| A/D | 0.6605 | likely_pathogenic | 0.6481 | pathogenic | -0.752 | Destabilizing | 0.011 | N | 0.328 | neutral | N | 0.464049906 | None | None | N |
| A/E | 0.5636 | ambiguous | 0.5572 | ambiguous | -0.91 | Destabilizing | 0.851 | D | 0.449 | neutral | None | None | None | None | N |
| A/F | 0.7178 | likely_pathogenic | 0.6939 | pathogenic | -1.013 | Destabilizing | 0.996 | D | 0.615 | neutral | None | None | None | None | N |
| A/G | 0.2791 | likely_benign | 0.2582 | benign | -0.459 | Destabilizing | 0.64 | D | 0.465 | neutral | N | 0.500511906 | None | None | N |
| A/H | 0.6717 | likely_pathogenic | 0.6938 | pathogenic | -0.536 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| A/I | 0.6663 | likely_pathogenic | 0.6241 | pathogenic | -0.416 | Destabilizing | 0.988 | D | 0.48 | neutral | None | None | None | None | N |
| A/K | 0.7812 | likely_pathogenic | 0.8008 | pathogenic | -0.809 | Destabilizing | 0.919 | D | 0.469 | neutral | None | None | None | None | N |
| A/L | 0.6045 | likely_pathogenic | 0.5668 | pathogenic | -0.416 | Destabilizing | 0.919 | D | 0.488 | neutral | None | None | None | None | N |
| A/M | 0.5359 | ambiguous | 0.5053 | ambiguous | -0.352 | Destabilizing | 0.999 | D | 0.483 | neutral | None | None | None | None | N |
| A/N | 0.4789 | ambiguous | 0.4529 | ambiguous | -0.407 | Destabilizing | 0.919 | D | 0.563 | neutral | None | None | None | None | N |
| A/P | 0.8959 | likely_pathogenic | 0.879 | pathogenic | -0.374 | Destabilizing | 0.984 | D | 0.457 | neutral | N | 0.463035948 | None | None | N |
| A/Q | 0.5525 | ambiguous | 0.5835 | pathogenic | -0.728 | Destabilizing | 0.988 | D | 0.477 | neutral | None | None | None | None | N |
| A/R | 0.7015 | likely_pathogenic | 0.7251 | pathogenic | -0.282 | Destabilizing | 0.976 | D | 0.476 | neutral | None | None | None | None | N |
| A/S | 0.1095 | likely_benign | 0.1086 | benign | -0.579 | Destabilizing | 0.103 | N | 0.281 | neutral | N | 0.493246709 | None | None | N |
| A/T | 0.2635 | likely_benign | 0.2333 | benign | -0.666 | Destabilizing | 0.811 | D | 0.441 | neutral | N | 0.476531847 | None | None | N |
| A/V | 0.3093 | likely_benign | 0.2816 | benign | -0.374 | Destabilizing | 0.896 | D | 0.439 | neutral | N | 0.485067156 | None | None | N |
| A/W | 0.9281 | likely_pathogenic | 0.9283 | pathogenic | -1.156 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/Y | 0.7324 | likely_pathogenic | 0.7225 | pathogenic | -0.816 | Destabilizing | 0.996 | D | 0.605 | neutral | None | None | 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.