Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32958 | 99097;99098;99099 | chr2:178539063;178539062;178539061 | chr2:179403790;179403789;179403788 |
| N2AB | 31317 | 94174;94175;94176 | chr2:178539063;178539062;178539061 | chr2:179403790;179403789;179403788 |
| N2A | 30390 | 91393;91394;91395 | chr2:178539063;178539062;178539061 | chr2:179403790;179403789;179403788 |
| N2B | 23893 | 71902;71903;71904 | chr2:178539063;178539062;178539061 | chr2:179403790;179403789;179403788 |
| Novex-1 | 24018 | 72277;72278;72279 | chr2:178539063;178539062;178539061 | chr2:179403790;179403789;179403788 |
| Novex-2 | 24085 | 72478;72479;72480 | chr2:178539063;178539062;178539061 | chr2:179403790;179403789;179403788 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1441902743  |
-0.004 | 0.999 | N | 0.664 | 0.416 | 0.614010665196 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| T/I | rs1441902743 |
-0.004 | 0.999 | N | 0.664 | 0.416 | 0.614010665196 | gnomAD-4.0.0 | 1.36844E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.799E-06 | 0 | 0 |
| T/S | rs1441902743 |
None | 0.989 | N | 0.438 | 0.316 | 0.31411915649 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs1441902743 |
None | 0.989 | N | 0.438 | 0.316 | 0.31411915649 | gnomAD-4.0.0 | 6.8422E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51915E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1749 | likely_benign | 0.1789 | benign | -0.848 | Destabilizing | 0.994 | D | 0.432 | neutral | N | 0.512329194 | None | None | N |
| T/C | 0.6121 | likely_pathogenic | 0.6203 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| T/D | 0.7967 | likely_pathogenic | 0.7815 | pathogenic | 0.172 | Stabilizing | 0.983 | D | 0.583 | neutral | None | None | None | None | N |
| T/E | 0.6837 | likely_pathogenic | 0.6638 | pathogenic | 0.167 | Stabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| T/F | 0.6283 | likely_pathogenic | 0.6433 | pathogenic | -1.054 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/G | 0.6295 | likely_pathogenic | 0.6315 | pathogenic | -1.083 | Destabilizing | 0.992 | D | 0.583 | neutral | None | None | None | None | N |
| T/H | 0.4887 | ambiguous | 0.4909 | ambiguous | -1.312 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/I | 0.3081 | likely_benign | 0.3068 | benign | -0.316 | Destabilizing | 0.999 | D | 0.664 | neutral | N | 0.52087132 | None | None | N |
| T/K | 0.5004 | ambiguous | 0.4788 | ambiguous | -0.526 | Destabilizing | 0.998 | D | 0.642 | neutral | None | None | None | None | N |
| T/L | 0.1868 | likely_benign | 0.1893 | benign | -0.316 | Destabilizing | 0.996 | D | 0.584 | neutral | None | None | None | None | N |
| T/M | 0.1347 | likely_benign | 0.1416 | benign | -0.089 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| T/N | 0.2581 | likely_benign | 0.2607 | benign | -0.474 | Destabilizing | 0.543 | D | 0.257 | neutral | N | 0.493396717 | None | None | N |
| T/P | 0.4305 | ambiguous | 0.4315 | ambiguous | -0.462 | Destabilizing | 0.999 | D | 0.666 | neutral | N | 0.511675834 | None | None | N |
| T/Q | 0.4293 | ambiguous | 0.4234 | ambiguous | -0.602 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| T/R | 0.4337 | ambiguous | 0.4043 | ambiguous | -0.325 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| T/S | 0.2362 | likely_benign | 0.2436 | benign | -0.8 | Destabilizing | 0.989 | D | 0.438 | neutral | N | 0.503093636 | None | None | N |
| T/V | 0.1994 | likely_benign | 0.2023 | benign | -0.462 | Destabilizing | 0.999 | D | 0.506 | neutral | None | None | None | None | N |
| T/W | 0.8928 | likely_pathogenic | 0.8945 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| T/Y | 0.6564 | likely_pathogenic | 0.6546 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | 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.