Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22380 | 67363;67364;67365 | chr2:178580149;178580148;178580147 | chr2:179444876;179444875;179444874 |
| N2AB | 20739 | 62440;62441;62442 | chr2:178580149;178580148;178580147 | chr2:179444876;179444875;179444874 |
| N2A | 19812 | 59659;59660;59661 | chr2:178580149;178580148;178580147 | chr2:179444876;179444875;179444874 |
| N2B | 13315 | 40168;40169;40170 | chr2:178580149;178580148;178580147 | chr2:179444876;179444875;179444874 |
| Novex-1 | 13440 | 40543;40544;40545 | chr2:178580149;178580148;178580147 | chr2:179444876;179444875;179444874 |
| Novex-2 | 13507 | 40744;40745;40746 | chr2:178580149;178580148;178580147 | chr2:179444876;179444875;179444874 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.317 | N | 0.333 | 0.105 | 0.385906861911 | gnomAD-4.0.0 | 6.84406E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99667E-07 | 0 | 0 |
| I/N | rs773461641  |
-0.146 | 0.188 | N | 0.479 | 0.323 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/N | rs773461641 |
-0.146 | 0.188 | N | 0.479 | 0.323 | None | gnomAD-4.0.0 | 1.36883E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79935E-06 | 0 | 0 |
| I/T | rs773461641 |
-0.557 | 0.062 | N | 0.34 | 0.214 | 0.468003879618 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.92E-06 | 0 |
| I/T | rs773461641 |
-0.557 | 0.062 | N | 0.34 | 0.214 | 0.468003879618 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.06954E-04 | 0 |
| I/T | rs773461641 |
-0.557 | 0.062 | N | 0.34 | 0.214 | 0.468003879618 | gnomAD-4.0.0 | 1.85964E-05 | None | None | None | None | I | None | 4.00652E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.94997E-05 | 2.19626E-05 | 3.20349E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4313 | ambiguous | 0.4863 | ambiguous | -0.663 | Destabilizing | 0.035 | N | 0.295 | neutral | None | None | None | None | I |
| I/C | 0.7866 | likely_pathogenic | 0.8133 | pathogenic | -0.697 | Destabilizing | 0.824 | D | 0.337 | neutral | None | None | None | None | I |
| I/D | 0.7807 | likely_pathogenic | 0.8152 | pathogenic | -0.115 | Destabilizing | 0.001 | N | 0.396 | neutral | None | None | None | None | I |
| I/E | 0.6929 | likely_pathogenic | 0.7433 | pathogenic | -0.197 | Destabilizing | 0.235 | N | 0.439 | neutral | None | None | None | None | I |
| I/F | 0.2649 | likely_benign | 0.3197 | benign | -0.614 | Destabilizing | 0.317 | N | 0.315 | neutral | N | 0.482285928 | None | None | I |
| I/G | 0.7966 | likely_pathogenic | 0.85 | pathogenic | -0.837 | Destabilizing | 0.38 | N | 0.438 | neutral | None | None | None | None | I |
| I/H | 0.6943 | likely_pathogenic | 0.7329 | pathogenic | -0.139 | Destabilizing | 0.935 | D | 0.443 | neutral | None | None | None | None | I |
| I/K | 0.6606 | likely_pathogenic | 0.7168 | pathogenic | -0.394 | Destabilizing | 0.38 | N | 0.459 | neutral | None | None | None | None | I |
| I/L | 0.1515 | likely_benign | 0.149 | benign | -0.324 | Destabilizing | None | N | 0.1 | neutral | N | 0.463006734 | None | None | I |
| I/M | 0.1355 | likely_benign | 0.1457 | benign | -0.421 | Destabilizing | 0.317 | N | 0.333 | neutral | N | 0.47955463 | None | None | I |
| I/N | 0.3187 | likely_benign | 0.3385 | benign | -0.218 | Destabilizing | 0.188 | N | 0.479 | neutral | N | 0.425931213 | None | None | I |
| I/P | 0.9315 | likely_pathogenic | 0.9464 | pathogenic | -0.403 | Destabilizing | 0.555 | D | 0.475 | neutral | None | None | None | None | I |
| I/Q | 0.6058 | likely_pathogenic | 0.6556 | pathogenic | -0.418 | Destabilizing | 0.555 | D | 0.461 | neutral | None | None | None | None | I |
| I/R | 0.521 | ambiguous | 0.5989 | pathogenic | 0.129 | Stabilizing | 0.555 | D | 0.464 | neutral | None | None | None | None | I |
| I/S | 0.3336 | likely_benign | 0.3907 | ambiguous | -0.689 | Destabilizing | 0.117 | N | 0.421 | neutral | N | 0.436974926 | None | None | I |
| I/T | 0.1875 | likely_benign | 0.2202 | benign | -0.659 | Destabilizing | 0.062 | N | 0.34 | neutral | N | 0.478168188 | None | None | I |
| I/V | 0.1113 | likely_benign | 0.1076 | benign | -0.403 | Destabilizing | None | N | 0.081 | neutral | N | 0.459486426 | None | None | I |
| I/W | 0.8323 | likely_pathogenic | 0.8651 | pathogenic | -0.632 | Destabilizing | 0.935 | D | 0.555 | neutral | None | None | None | None | I |
| I/Y | 0.6027 | likely_pathogenic | 0.6687 | pathogenic | -0.388 | Destabilizing | 0.555 | D | 0.333 | 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.