Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26819 | 80680;80681;80682 | chr2:178565677;178565676;178565675 | chr2:179430404;179430403;179430402 |
| N2AB | 25178 | 75757;75758;75759 | chr2:178565677;178565676;178565675 | chr2:179430404;179430403;179430402 |
| N2A | 24251 | 72976;72977;72978 | chr2:178565677;178565676;178565675 | chr2:179430404;179430403;179430402 |
| N2B | 17754 | 53485;53486;53487 | chr2:178565677;178565676;178565675 | chr2:179430404;179430403;179430402 |
| Novex-1 | 17879 | 53860;53861;53862 | chr2:178565677;178565676;178565675 | chr2:179430404;179430403;179430402 |
| Novex-2 | 17946 | 54061;54062;54063 | chr2:178565677;178565676;178565675 | chr2:179430404;179430403;179430402 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs749446343  |
0.408 | 0.847 | N | 0.595 | 0.261 | 0.384752662912 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 0 |
| M/I | rs749446343 |
0.408 | 0.847 | N | 0.595 | 0.261 | 0.384752662912 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| M/I | rs749446343 |
0.408 | 0.847 | N | 0.595 | 0.261 | 0.384752662912 | gnomAD-4.0.0 | 2.69098E-05 | None | None | None | None | N | None | 0 | 1.69515E-05 | None | 0 | 0 | None | 0 | 0 | 4.54824E-05 | 0 | 2.84544E-05 |
| M/L | rs1705523531 |
None | 0.333 | N | 0.459 | 0.301 | 0.416833835346 | gnomAD-4.0.0 | 1.59158E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85919E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7432 | likely_pathogenic | 0.7455 | pathogenic | -1.498 | Destabilizing | 0.942 | D | 0.555 | neutral | None | None | None | None | N |
| M/C | 0.7911 | likely_pathogenic | 0.8018 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| M/D | 0.994 | likely_pathogenic | 0.9942 | pathogenic | -1.569 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | N |
| M/E | 0.9345 | likely_pathogenic | 0.9312 | pathogenic | -1.291 | Destabilizing | 0.972 | D | 0.675 | prob.neutral | None | None | None | None | N |
| M/F | 0.4227 | ambiguous | 0.4359 | ambiguous | -0.238 | Destabilizing | 0.481 | N | 0.609 | neutral | None | None | None | None | N |
| M/G | 0.8838 | likely_pathogenic | 0.8887 | pathogenic | -2.014 | Highly Destabilizing | 0.988 | D | 0.691 | prob.neutral | None | None | None | None | N |
| M/H | 0.8693 | likely_pathogenic | 0.8691 | pathogenic | -1.978 | Destabilizing | 0.983 | D | 0.707 | prob.neutral | None | None | None | None | N |
| M/I | 0.724 | likely_pathogenic | 0.6831 | pathogenic | -0.005 | Destabilizing | 0.847 | D | 0.595 | neutral | N | 0.462009444 | None | None | N |
| M/K | 0.5244 | ambiguous | 0.5093 | ambiguous | -0.722 | Destabilizing | 0.918 | D | 0.594 | neutral | N | 0.428243587 | None | None | N |
| M/L | 0.2958 | likely_benign | 0.2838 | benign | -0.005 | Destabilizing | 0.333 | N | 0.459 | neutral | N | 0.451368375 | None | None | N |
| M/N | 0.9269 | likely_pathogenic | 0.9318 | pathogenic | -1.283 | Destabilizing | 0.988 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/P | 0.9986 | likely_pathogenic | 0.9987 | pathogenic | -0.485 | Destabilizing | 0.996 | D | 0.696 | prob.neutral | None | None | None | None | N |
| M/Q | 0.6067 | likely_pathogenic | 0.6183 | pathogenic | -0.828 | Destabilizing | 0.992 | D | 0.63 | neutral | None | None | None | None | N |
| M/R | 0.5942 | likely_pathogenic | 0.5799 | pathogenic | -1.181 | Destabilizing | 0.988 | D | 0.675 | prob.neutral | N | 0.444117116 | None | None | N |
| M/S | 0.7877 | likely_pathogenic | 0.802 | pathogenic | -1.751 | Destabilizing | 0.988 | D | 0.601 | neutral | None | None | None | None | N |
| M/T | 0.6971 | likely_pathogenic | 0.731 | pathogenic | -1.328 | Destabilizing | 0.948 | D | 0.591 | neutral | N | 0.512360906 | None | None | N |
| M/V | 0.2929 | likely_benign | 0.2777 | benign | -0.485 | Destabilizing | 0.837 | D | 0.55 | neutral | N | 0.459449141 | None | None | N |
| M/W | 0.8596 | likely_pathogenic | 0.8726 | pathogenic | -0.67 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| M/Y | 0.668 | likely_pathogenic | 0.6986 | pathogenic | -0.524 | Destabilizing | 0.065 | N | 0.409 | 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.