Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23391 | 70396;70397;70398 | chr2:178575961;178575960;178575959 | chr2:179440688;179440687;179440686 |
| N2AB | 21750 | 65473;65474;65475 | chr2:178575961;178575960;178575959 | chr2:179440688;179440687;179440686 |
| N2A | 20823 | 62692;62693;62694 | chr2:178575961;178575960;178575959 | chr2:179440688;179440687;179440686 |
| N2B | 14326 | 43201;43202;43203 | chr2:178575961;178575960;178575959 | chr2:179440688;179440687;179440686 |
| Novex-1 | 14451 | 43576;43577;43578 | chr2:178575961;178575960;178575959 | chr2:179440688;179440687;179440686 |
| Novex-2 | 14518 | 43777;43778;43779 | chr2:178575961;178575960;178575959 | chr2:179440688;179440687;179440686 |
| 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 | rs1376271320  |
-0.866 | 0.99 | N | 0.449 | 0.438 | 0.516217604878 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs1376271320 |
-0.866 | 0.99 | N | 0.449 | 0.438 | 0.516217604878 | gnomAD-4.0.0 | 1.59691E-06 | None | None | None | None | N | None | 5.67086E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | None | None | 0.014 | D | 0.445 | 0.503 | 0.71446170501 | gnomAD-4.0.0 | 6.85241E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00961E-07 | 0 | 0 |
| I/T | rs375202101 |
-2.038 | 0.822 | N | 0.457 | 0.45 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 8.28E-05 | 5.66E-05 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/T | rs375202101 |
-2.038 | 0.822 | N | 0.457 | 0.45 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 1.2068E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs375202101 |
-2.038 | 0.822 | N | 0.457 | 0.45 | None | gnomAD-4.0.0 | 2.29615E-05 | None | None | None | None | N | None | 1.20234E-04 | 6.67379E-05 | None | 0 | 4.46568E-05 | None | 0 | 0 | 1.78282E-05 | 0 | 1.60292E-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 | 0.5615 | ambiguous | 0.5893 | pathogenic | -2.261 | Highly Destabilizing | 0.86 | D | 0.417 | neutral | None | None | None | None | N |
| I/C | 0.8731 | likely_pathogenic | 0.8935 | pathogenic | -1.319 | Destabilizing | 0.998 | D | 0.525 | neutral | None | None | None | None | N |
| I/D | 0.9723 | likely_pathogenic | 0.9781 | pathogenic | -2.043 | Highly Destabilizing | 0.915 | D | 0.644 | neutral | None | None | None | None | N |
| I/E | 0.8765 | likely_pathogenic | 0.8934 | pathogenic | -1.974 | Destabilizing | 0.956 | D | 0.648 | neutral | None | None | None | None | N |
| I/F | 0.4423 | ambiguous | 0.4898 | ambiguous | -1.513 | Destabilizing | 0.99 | D | 0.427 | neutral | N | 0.48686178 | None | None | N |
| I/G | 0.9379 | likely_pathogenic | 0.9493 | pathogenic | -2.67 | Highly Destabilizing | 0.754 | D | 0.623 | neutral | None | None | None | None | N |
| I/H | 0.8895 | likely_pathogenic | 0.9134 | pathogenic | -1.934 | Destabilizing | 0.994 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/K | 0.7849 | likely_pathogenic | 0.8194 | pathogenic | -1.717 | Destabilizing | 0.956 | D | 0.657 | neutral | None | None | None | None | N |
| I/L | 0.2507 | likely_benign | 0.2666 | benign | -1.15 | Destabilizing | 0.795 | D | 0.363 | neutral | N | 0.508297173 | None | None | N |
| I/M | 0.1694 | likely_benign | 0.1863 | benign | -0.817 | Destabilizing | 0.99 | D | 0.449 | neutral | N | 0.485847822 | None | None | N |
| I/N | 0.8222 | likely_pathogenic | 0.845 | pathogenic | -1.583 | Destabilizing | 0.014 | N | 0.445 | neutral | D | 0.532086418 | None | None | N |
| I/P | 0.9593 | likely_pathogenic | 0.9649 | pathogenic | -1.493 | Destabilizing | 0.993 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8107 | likely_pathogenic | 0.8343 | pathogenic | -1.698 | Destabilizing | 0.956 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/R | 0.6932 | likely_pathogenic | 0.7344 | pathogenic | -1.12 | Destabilizing | 0.956 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/S | 0.6769 | likely_pathogenic | 0.7076 | pathogenic | -2.218 | Highly Destabilizing | 0.698 | D | 0.53 | neutral | N | 0.501865389 | None | None | N |
| I/T | 0.2441 | likely_benign | 0.2457 | benign | -2.029 | Highly Destabilizing | 0.822 | D | 0.457 | neutral | N | 0.492800035 | None | None | N |
| I/V | 0.086 | likely_benign | 0.0958 | benign | -1.493 | Destabilizing | 0.795 | D | 0.4 | neutral | N | 0.486321603 | None | None | N |
| I/W | 0.924 | likely_pathogenic | 0.9421 | pathogenic | -1.696 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | N |
| I/Y | 0.84 | likely_pathogenic | 0.8726 | pathogenic | -1.496 | Destabilizing | 0.993 | D | 0.505 | 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.