Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21596 | 65011;65012;65013 | chr2:178584855;178584854;178584853 | chr2:179449582;179449581;179449580 |
| N2AB | 19955 | 60088;60089;60090 | chr2:178584855;178584854;178584853 | chr2:179449582;179449581;179449580 |
| N2A | 19028 | 57307;57308;57309 | chr2:178584855;178584854;178584853 | chr2:179449582;179449581;179449580 |
| N2B | 12531 | 37816;37817;37818 | chr2:178584855;178584854;178584853 | chr2:179449582;179449581;179449580 |
| Novex-1 | 12656 | 38191;38192;38193 | chr2:178584855;178584854;178584853 | chr2:179449582;179449581;179449580 |
| Novex-2 | 12723 | 38392;38393;38394 | chr2:178584855;178584854;178584853 | chr2:179449582;179449581;179449580 |
| 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/R | None | None | 0.667 | N | 0.703 | 0.465 | 0.779246962076 | gnomAD-4.0.0 | 6.84363E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99635E-07 | 0 | 0 |
| I/T | rs779333272  |
-2.826 | 0.124 | N | 0.57 | 0.267 | 0.646260075106 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/T | rs779333272 |
-2.826 | 0.124 | N | 0.57 | 0.267 | 0.646260075106 | gnomAD-4.0.0 | 6.84363E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52181E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.547 | ambiguous | 0.6433 | pathogenic | -2.607 | Highly Destabilizing | 0.072 | N | 0.537 | neutral | None | None | None | None | I |
| I/C | 0.8206 | likely_pathogenic | 0.8453 | pathogenic | -2.059 | Highly Destabilizing | 0.909 | D | 0.649 | neutral | None | None | None | None | I |
| I/D | 0.9571 | likely_pathogenic | 0.9738 | pathogenic | -3.193 | Highly Destabilizing | 0.726 | D | 0.685 | prob.neutral | None | None | None | None | I |
| I/E | 0.8796 | likely_pathogenic | 0.9142 | pathogenic | -3.054 | Highly Destabilizing | 0.726 | D | 0.683 | prob.neutral | None | None | None | None | I |
| I/F | 0.4493 | ambiguous | 0.4809 | ambiguous | -1.603 | Destabilizing | 0.567 | D | 0.606 | neutral | None | None | None | None | I |
| I/G | 0.9162 | likely_pathogenic | 0.9417 | pathogenic | -3.051 | Highly Destabilizing | 0.726 | D | 0.668 | neutral | None | None | None | None | I |
| I/H | 0.8052 | likely_pathogenic | 0.8452 | pathogenic | -2.327 | Highly Destabilizing | 0.968 | D | 0.704 | prob.neutral | None | None | None | None | I |
| I/K | 0.7643 | likely_pathogenic | 0.8181 | pathogenic | -2.029 | Highly Destabilizing | 0.667 | D | 0.683 | prob.neutral | N | 0.477290132 | None | None | I |
| I/L | 0.2476 | likely_benign | 0.2665 | benign | -1.348 | Destabilizing | 0.025 | N | 0.389 | neutral | N | 0.4690117 | None | None | I |
| I/M | 0.1945 | likely_benign | 0.2169 | benign | -1.352 | Destabilizing | 0.497 | N | 0.625 | neutral | N | 0.497208494 | None | None | I |
| I/N | 0.6805 | likely_pathogenic | 0.752 | pathogenic | -2.232 | Highly Destabilizing | 0.89 | D | 0.701 | prob.neutral | None | None | None | None | I |
| I/P | 0.9903 | likely_pathogenic | 0.9946 | pathogenic | -1.748 | Destabilizing | 0.89 | D | 0.686 | prob.neutral | None | None | None | None | I |
| I/Q | 0.7687 | likely_pathogenic | 0.8176 | pathogenic | -2.259 | Highly Destabilizing | 0.89 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/R | 0.6668 | likely_pathogenic | 0.7265 | pathogenic | -1.51 | Destabilizing | 0.667 | D | 0.703 | prob.neutral | N | 0.471667819 | None | None | I |
| I/S | 0.5369 | ambiguous | 0.6403 | pathogenic | -2.829 | Highly Destabilizing | 0.567 | D | 0.63 | neutral | None | None | None | None | I |
| I/T | 0.2401 | likely_benign | 0.3032 | benign | -2.572 | Highly Destabilizing | 0.124 | N | 0.57 | neutral | N | 0.504568142 | None | None | I |
| I/V | 0.0622 | likely_benign | 0.0692 | benign | -1.748 | Destabilizing | None | N | 0.229 | neutral | N | 0.462433518 | None | None | I |
| I/W | 0.9431 | likely_pathogenic | 0.9477 | pathogenic | -1.922 | Destabilizing | 0.968 | D | 0.707 | prob.neutral | None | None | None | None | I |
| I/Y | 0.8157 | likely_pathogenic | 0.8421 | pathogenic | -1.713 | Destabilizing | 0.726 | D | 0.648 | neutral | None | None | None | None | I |
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.