Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23175 | 69748;69749;69750 | chr2:178576721;178576720;178576719 | chr2:179441448;179441447;179441446 |
| N2AB | 21534 | 64825;64826;64827 | chr2:178576721;178576720;178576719 | chr2:179441448;179441447;179441446 |
| N2A | 20607 | 62044;62045;62046 | chr2:178576721;178576720;178576719 | chr2:179441448;179441447;179441446 |
| N2B | 14110 | 42553;42554;42555 | chr2:178576721;178576720;178576719 | chr2:179441448;179441447;179441446 |
| Novex-1 | 14235 | 42928;42929;42930 | chr2:178576721;178576720;178576719 | chr2:179441448;179441447;179441446 |
| Novex-2 | 14302 | 43129;43130;43131 | chr2:178576721;178576720;178576719 | chr2:179441448;179441447;179441446 |
| 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/N | None | None | 0.491 | N | 0.562 | 0.061 | 0.219573609325 | gnomAD-4.0.0 | 1.59167E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85922E-06 | 0 | 0 |
| H/P | None | None | 0.873 | N | 0.689 | 0.294 | 0.343101102393 | gnomAD-4.0.0 | 1.36878E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79946E-06 | 0 | 0 |
| H/R | rs1186507360  |
-1.87 | 0.662 | N | 0.599 | 0.174 | 0.234412748748 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/R | rs1186507360 |
-1.87 | 0.662 | N | 0.599 | 0.174 | 0.234412748748 | gnomAD-4.0.0 | 1.36873E-06 | None | None | None | None | N | None | 2.99025E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65706E-05 |
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 | 0.4831 | ambiguous | 0.4936 | ambiguous | -1.359 | Destabilizing | 0.103 | N | 0.581 | neutral | None | None | None | None | N |
| H/C | 0.1582 | likely_benign | 0.172 | benign | -0.698 | Destabilizing | 0.002 | N | 0.561 | neutral | None | None | None | None | N |
| H/D | 0.6481 | likely_pathogenic | 0.7052 | pathogenic | -1.15 | Destabilizing | 0.491 | N | 0.648 | neutral | N | 0.459219854 | None | None | N |
| H/E | 0.6113 | likely_pathogenic | 0.6484 | pathogenic | -1.018 | Destabilizing | 0.561 | D | 0.537 | neutral | None | None | None | None | N |
| H/F | 0.167 | likely_benign | 0.1659 | benign | 0.128 | Stabilizing | 0.39 | N | 0.646 | neutral | None | None | None | None | N |
| H/G | 0.6993 | likely_pathogenic | 0.7298 | pathogenic | -1.719 | Destabilizing | 0.345 | N | 0.61 | neutral | None | None | None | None | N |
| H/I | 0.1788 | likely_benign | 0.1669 | benign | -0.333 | Destabilizing | 0.002 | N | 0.566 | neutral | None | None | None | None | N |
| H/K | 0.5219 | ambiguous | 0.5633 | ambiguous | -1.186 | Destabilizing | 0.561 | D | 0.637 | neutral | None | None | None | None | N |
| H/L | 0.1223 | likely_benign | 0.1261 | benign | -0.333 | Destabilizing | 0.029 | N | 0.609 | neutral | N | 0.398075395 | None | None | N |
| H/M | 0.4194 | ambiguous | 0.3973 | ambiguous | -0.562 | Destabilizing | 0.818 | D | 0.679 | prob.neutral | None | None | None | None | N |
| H/N | 0.2113 | likely_benign | 0.2299 | benign | -1.339 | Destabilizing | 0.491 | N | 0.562 | neutral | N | 0.43732443 | None | None | N |
| H/P | 0.915 | likely_pathogenic | 0.9368 | pathogenic | -0.66 | Destabilizing | 0.873 | D | 0.689 | prob.neutral | N | 0.468393043 | None | None | N |
| H/Q | 0.3154 | likely_benign | 0.3315 | benign | -1.011 | Destabilizing | 0.662 | D | 0.621 | neutral | N | 0.443519683 | None | None | N |
| H/R | 0.2243 | likely_benign | 0.2582 | benign | -1.511 | Destabilizing | 0.662 | D | 0.599 | neutral | N | 0.434225409 | None | None | N |
| H/S | 0.3822 | ambiguous | 0.3993 | ambiguous | -1.433 | Destabilizing | 0.021 | N | 0.402 | neutral | None | None | None | None | N |
| H/T | 0.3714 | ambiguous | 0.3698 | ambiguous | -1.206 | Destabilizing | 0.209 | N | 0.611 | neutral | None | None | None | None | N |
| H/V | 0.18 | likely_benign | 0.1751 | benign | -0.66 | Destabilizing | 0.083 | N | 0.619 | neutral | None | None | None | None | N |
| H/W | 0.2554 | likely_benign | 0.2648 | benign | 0.467 | Stabilizing | 0.972 | D | 0.685 | prob.neutral | None | None | None | None | N |
| H/Y | 0.069 | likely_benign | 0.0711 | benign | 0.474 | Stabilizing | 0.003 | N | 0.27 | neutral | N | 0.432612043 | 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.