Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17436 | 52531;52532;52533 | chr2:178608705;178608704;178608703 | chr2:179473432;179473431;179473430 |
| N2AB | 15795 | 47608;47609;47610 | chr2:178608705;178608704;178608703 | chr2:179473432;179473431;179473430 |
| N2A | 14868 | 44827;44828;44829 | chr2:178608705;178608704;178608703 | chr2:179473432;179473431;179473430 |
| N2B | 8371 | 25336;25337;25338 | chr2:178608705;178608704;178608703 | chr2:179473432;179473431;179473430 |
| Novex-1 | 8496 | 25711;25712;25713 | chr2:178608705;178608704;178608703 | chr2:179473432;179473431;179473430 |
| Novex-2 | 8563 | 25912;25913;25914 | chr2:178608705;178608704;178608703 | chr2:179473432;179473431;179473430 |
| 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 | 0.983 | N | 0.469 | 0.245 | 0.382087116544 | gnomAD-4.0.0 | 6.84743E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99891E-07 | 0 | 0 |
| I/T | rs774439701  |
-0.855 | 0.025 | N | 0.25 | 0.228 | 0.37550373646 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs774439701 |
-0.855 | 0.025 | N | 0.25 | 0.228 | 0.37550373646 | gnomAD-4.0.0 | 9.58649E-06 | None | None | None | None | N | None | 2.99365E-05 | 0 | None | 0 | 7.60803E-05 | None | 0 | 0 | 2.69968E-06 | 8.11971E-05 | 0 |
| I/V | None | None | 0.426 | N | 0.304 | 0.18 | 0.347438807231 | gnomAD-4.0.0 | 1.59418E-06 | None | None | None | None | N | None | 0 | 2.29064E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2938 | likely_benign | 0.2978 | benign | -1.269 | Destabilizing | 0.845 | D | 0.44 | neutral | None | None | None | None | N |
| I/C | 0.7693 | likely_pathogenic | 0.803 | pathogenic | -0.87 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| I/D | 0.8293 | likely_pathogenic | 0.8425 | pathogenic | -0.414 | Destabilizing | 0.975 | D | 0.645 | neutral | None | None | None | None | N |
| I/E | 0.5702 | likely_pathogenic | 0.5888 | pathogenic | -0.421 | Destabilizing | 0.975 | D | 0.645 | neutral | None | None | None | None | N |
| I/F | 0.2639 | likely_benign | 0.2854 | benign | -0.831 | Destabilizing | 0.983 | D | 0.477 | neutral | N | 0.51016875 | None | None | N |
| I/G | 0.7226 | likely_pathogenic | 0.7258 | pathogenic | -1.557 | Destabilizing | 0.975 | D | 0.612 | neutral | None | None | None | None | N |
| I/H | 0.5769 | likely_pathogenic | 0.6001 | pathogenic | -0.602 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| I/K | 0.4384 | ambiguous | 0.4531 | ambiguous | -0.755 | Destabilizing | 0.975 | D | 0.644 | neutral | None | None | None | None | N |
| I/L | 0.1166 | likely_benign | 0.111 | benign | -0.572 | Destabilizing | 0.63 | D | 0.315 | neutral | N | 0.486790458 | None | None | N |
| I/M | 0.0971 | likely_benign | 0.0982 | benign | -0.579 | Destabilizing | 0.983 | D | 0.469 | neutral | N | 0.502357343 | None | None | N |
| I/N | 0.4338 | ambiguous | 0.456 | ambiguous | -0.616 | Destabilizing | 0.967 | D | 0.65 | neutral | N | 0.489465404 | None | None | N |
| I/P | 0.8357 | likely_pathogenic | 0.8449 | pathogenic | -0.771 | Destabilizing | 0.987 | D | 0.647 | neutral | None | None | None | None | N |
| I/Q | 0.3968 | ambiguous | 0.3937 | ambiguous | -0.762 | Destabilizing | 0.987 | D | 0.645 | neutral | None | None | None | None | N |
| I/R | 0.3355 | likely_benign | 0.3543 | ambiguous | -0.187 | Destabilizing | 0.975 | D | 0.641 | neutral | None | None | None | None | N |
| I/S | 0.3358 | likely_benign | 0.3466 | ambiguous | -1.241 | Destabilizing | 0.805 | D | 0.474 | neutral | N | 0.47430395 | None | None | N |
| I/T | 0.1348 | likely_benign | 0.1457 | benign | -1.123 | Destabilizing | 0.025 | N | 0.25 | neutral | N | 0.414178211 | None | None | N |
| I/V | 0.1131 | likely_benign | 0.1185 | benign | -0.771 | Destabilizing | 0.426 | N | 0.304 | neutral | N | 0.439730017 | None | None | N |
| I/W | 0.7573 | likely_pathogenic | 0.7579 | pathogenic | -0.85 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| I/Y | 0.6324 | likely_pathogenic | 0.6537 | pathogenic | -0.628 | Destabilizing | 0.996 | D | 0.539 | 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.