Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2746 | 8461;8462;8463 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
| N2AB | 2746 | 8461;8462;8463 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
| N2A | 2746 | 8461;8462;8463 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
| N2B | 2700 | 8323;8324;8325 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
| Novex-1 | 2700 | 8323;8324;8325 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
| Novex-2 | 2700 | 8323;8324;8325 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
| Novex-3 | 2746 | 8461;8462;8463 | chr2:178770556;178770555;178770554 | chr2:179635283;179635282;179635281 |
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/L | rs1056269539  |
None | None | N | 0.148 | 0.087 | 0.450152462452 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1056269539 |
None | None | N | 0.148 | 0.087 | 0.450152462452 | gnomAD-4.0.0 | 6.57108E-06 | None | None | None | None | N | None | 2.41313E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0956 | likely_benign | 0.1241 | benign | -0.82 | Destabilizing | None | N | 0.141 | neutral | N | 0.503505563 | None | None | N |
| V/C | 0.615 | likely_pathogenic | 0.7096 | pathogenic | -0.738 | Destabilizing | 0.356 | N | 0.377 | neutral | None | None | None | None | N |
| V/D | 0.1787 | likely_benign | 0.2451 | benign | -0.597 | Destabilizing | 0.016 | N | 0.372 | neutral | None | None | None | None | N |
| V/E | 0.0952 | likely_benign | 0.1305 | benign | -0.669 | Destabilizing | None | N | 0.153 | neutral | N | 0.355876978 | None | None | N |
| V/F | 0.1275 | likely_benign | 0.1604 | benign | -0.754 | Destabilizing | 0.214 | N | 0.452 | neutral | None | None | None | None | N |
| V/G | 0.1447 | likely_benign | 0.2028 | benign | -1.023 | Destabilizing | 0.012 | N | 0.381 | neutral | N | 0.505657197 | None | None | N |
| V/H | 0.3465 | ambiguous | 0.4376 | ambiguous | -0.517 | Destabilizing | 0.356 | N | 0.443 | neutral | None | None | None | None | N |
| V/I | 0.074 | likely_benign | 0.0734 | benign | -0.41 | Destabilizing | 0.016 | N | 0.27 | neutral | None | None | None | None | N |
| V/K | 0.1527 | likely_benign | 0.199 | benign | -0.837 | Destabilizing | 0.016 | N | 0.357 | neutral | None | None | None | None | N |
| V/L | 0.0998 | likely_benign | 0.1321 | benign | -0.41 | Destabilizing | None | N | 0.148 | neutral | N | 0.493644121 | None | None | N |
| V/M | 0.0963 | likely_benign | 0.1082 | benign | -0.445 | Destabilizing | 0.001 | N | 0.217 | neutral | N | 0.505657197 | None | None | N |
| V/N | 0.1483 | likely_benign | 0.1894 | benign | -0.606 | Destabilizing | 0.072 | N | 0.467 | neutral | None | None | None | None | N |
| V/P | 0.1619 | likely_benign | 0.2217 | benign | -0.511 | Destabilizing | 0.072 | N | 0.453 | neutral | None | None | None | None | N |
| V/Q | 0.1419 | likely_benign | 0.191 | benign | -0.818 | Destabilizing | 0.038 | N | 0.419 | neutral | None | None | None | None | N |
| V/R | 0.1717 | likely_benign | 0.2174 | benign | -0.279 | Destabilizing | 0.072 | N | 0.439 | neutral | None | None | None | None | N |
| V/S | 0.1198 | likely_benign | 0.1587 | benign | -1.003 | Destabilizing | 0.016 | N | 0.347 | neutral | None | None | None | None | N |
| V/T | 0.1154 | likely_benign | 0.1431 | benign | -0.975 | Destabilizing | 0.016 | N | 0.241 | neutral | None | None | None | None | N |
| V/W | 0.6389 | likely_pathogenic | 0.7617 | pathogenic | -0.87 | Destabilizing | 0.864 | D | 0.432 | neutral | None | None | None | None | N |
| V/Y | 0.388 | ambiguous | 0.4935 | ambiguous | -0.593 | Destabilizing | 0.356 | N | 0.445 | 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.