Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32535 | 97828;97829;97830 | chr2:178541474;178541473;178541472 | chr2:179406201;179406200;179406199 |
| N2AB | 30894 | 92905;92906;92907 | chr2:178541474;178541473;178541472 | chr2:179406201;179406200;179406199 |
| N2A | 29967 | 90124;90125;90126 | chr2:178541474;178541473;178541472 | chr2:179406201;179406200;179406199 |
| N2B | 23470 | 70633;70634;70635 | chr2:178541474;178541473;178541472 | chr2:179406201;179406200;179406199 |
| Novex-1 | 23595 | 71008;71009;71010 | chr2:178541474;178541473;178541472 | chr2:179406201;179406200;179406199 |
| Novex-2 | 23662 | 71209;71210;71211 | chr2:178541474;178541473;178541472 | chr2:179406201;179406200;179406199 |
| 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 | rs760676361  |
-1.245 | 1.0 | N | 0.747 | 0.25 | 0.539612970712 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 0 |
| I/M | rs760676361 |
-1.245 | 1.0 | N | 0.747 | 0.25 | 0.539612970712 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs760676361 |
-1.245 | 1.0 | N | 0.747 | 0.25 | 0.539612970712 | gnomAD-4.0.0 | 4.89659E-05 | None | None | None | None | N | None | 4.00652E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.3581E-05 | 0 | 1.60169E-05 |
| I/T | rs2154141649 |
None | 1.0 | N | 0.701 | 0.475 | 0.731403993514 | gnomAD-4.0.0 | 1.36871E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15977E-05 | 1.65717E-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 | 0.4108 | ambiguous | 0.377 | ambiguous | -2.512 | Highly Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| I/C | 0.7632 | likely_pathogenic | 0.7136 | pathogenic | -1.748 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/D | 0.8586 | likely_pathogenic | 0.8507 | pathogenic | -2.846 | Highly Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| I/E | 0.7821 | likely_pathogenic | 0.7648 | pathogenic | -2.735 | Highly Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| I/F | 0.1487 | likely_benign | 0.139 | benign | -1.6 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.507667162 | None | None | N |
| I/G | 0.8532 | likely_pathogenic | 0.7997 | pathogenic | -2.936 | Highly Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/H | 0.5462 | ambiguous | 0.5289 | ambiguous | -2.195 | Highly Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/K | 0.7506 | likely_pathogenic | 0.719 | pathogenic | -1.985 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| I/L | 0.1138 | likely_benign | 0.107 | benign | -1.331 | Destabilizing | 0.993 | D | 0.395 | neutral | N | 0.496026017 | None | None | N |
| I/M | 0.1077 | likely_benign | 0.0987 | benign | -1.143 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.518422874 | None | None | N |
| I/N | 0.4721 | ambiguous | 0.4447 | ambiguous | -2.07 | Highly Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.516419931 | None | None | N |
| I/P | 0.9862 | likely_pathogenic | 0.9815 | pathogenic | -1.703 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/Q | 0.6719 | likely_pathogenic | 0.6365 | pathogenic | -2.143 | Highly Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/R | 0.6194 | likely_pathogenic | 0.5746 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/S | 0.435 | ambiguous | 0.3937 | ambiguous | -2.674 | Highly Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.462628918 | None | None | N |
| I/T | 0.2052 | likely_benign | 0.2028 | benign | -2.453 | Highly Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.492716353 | None | None | N |
| I/V | 0.0842 | likely_benign | 0.0793 | benign | -1.703 | Destabilizing | 0.993 | D | 0.396 | neutral | N | 0.4573157 | None | None | N |
| I/W | 0.7012 | likely_pathogenic | 0.6858 | pathogenic | -1.881 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Y | 0.481 | ambiguous | 0.4641 | ambiguous | -1.677 | Destabilizing | 1.0 | D | 0.747 | deleterious | 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.