Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13705 | 41338;41339;41340 | chr2:178636614;178636613;178636612 | chr2:179501341;179501340;179501339 |
| N2AB | 12064 | 36415;36416;36417 | chr2:178636614;178636613;178636612 | chr2:179501341;179501340;179501339 |
| N2A | 11137 | 33634;33635;33636 | chr2:178636614;178636613;178636612 | chr2:179501341;179501340;179501339 |
| N2B | 4640 | 14143;14144;14145 | chr2:178636614;178636613;178636612 | chr2:179501341;179501340;179501339 |
| Novex-1 | 4765 | 14518;14519;14520 | chr2:178636614;178636613;178636612 | chr2:179501341;179501340;179501339 |
| Novex-2 | 4832 | 14719;14720;14721 | chr2:178636614;178636613;178636612 | chr2:179501341;179501340;179501339 |
| 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/F | None | None | 0.934 | N | 0.557 | 0.189 | 0.340032825777 | gnomAD-4.0.0 | 6.84351E-07 | None | None | None | None | N | None | 2.98864E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.051 | N | 0.403 | 0.201 | 0.426551566703 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | rs769704113  |
-1.401 | 0.005 | N | 0.29 | 0.045 | 0.319114376414 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12082E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs769704113 |
-1.401 | 0.005 | N | 0.29 | 0.045 | 0.319114376414 | gnomAD-4.0.0 | 4.79046E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.05076E-05 | None | 0 | 0 | 2.6988E-06 | 2.31889E-05 | 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 | 0.7984 | likely_pathogenic | 0.8374 | pathogenic | -1.898 | Destabilizing | 0.525 | D | 0.523 | neutral | None | None | None | None | N |
| I/C | 0.9621 | likely_pathogenic | 0.9649 | pathogenic | -1.016 | Destabilizing | 0.998 | D | 0.579 | neutral | None | None | None | None | N |
| I/D | 0.9747 | likely_pathogenic | 0.982 | pathogenic | -1.259 | Destabilizing | 0.974 | D | 0.663 | neutral | None | None | None | None | N |
| I/E | 0.9421 | likely_pathogenic | 0.9535 | pathogenic | -1.17 | Destabilizing | 0.974 | D | 0.659 | neutral | None | None | None | None | N |
| I/F | 0.5997 | likely_pathogenic | 0.643 | pathogenic | -1.145 | Destabilizing | 0.934 | D | 0.557 | neutral | N | 0.452368666 | None | None | N |
| I/G | 0.9724 | likely_pathogenic | 0.979 | pathogenic | -2.306 | Highly Destabilizing | 0.915 | D | 0.637 | neutral | None | None | None | None | N |
| I/H | 0.9397 | likely_pathogenic | 0.9475 | pathogenic | -1.407 | Destabilizing | 0.998 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/K | 0.9249 | likely_pathogenic | 0.9313 | pathogenic | -1.235 | Destabilizing | 0.974 | D | 0.658 | neutral | None | None | None | None | N |
| I/L | 0.3464 | ambiguous | 0.3819 | ambiguous | -0.802 | Destabilizing | 0.267 | N | 0.491 | neutral | N | 0.442113574 | None | None | N |
| I/M | 0.3574 | ambiguous | 0.3738 | ambiguous | -0.629 | Destabilizing | 0.966 | D | 0.578 | neutral | N | 0.452095135 | None | None | N |
| I/N | 0.7987 | likely_pathogenic | 0.8291 | pathogenic | -1.159 | Destabilizing | 0.966 | D | 0.677 | prob.neutral | N | 0.450496318 | None | None | N |
| I/P | 0.9914 | likely_pathogenic | 0.9945 | pathogenic | -1.139 | Destabilizing | 0.991 | D | 0.674 | neutral | None | None | None | None | N |
| I/Q | 0.9128 | likely_pathogenic | 0.924 | pathogenic | -1.217 | Destabilizing | 0.991 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/R | 0.889 | likely_pathogenic | 0.9023 | pathogenic | -0.747 | Destabilizing | 0.974 | D | 0.67 | neutral | None | None | None | None | N |
| I/S | 0.7631 | likely_pathogenic | 0.7909 | pathogenic | -1.855 | Destabilizing | 0.669 | D | 0.554 | neutral | N | 0.438493819 | None | None | N |
| I/T | 0.581 | likely_pathogenic | 0.5937 | pathogenic | -1.633 | Destabilizing | 0.051 | N | 0.403 | neutral | N | 0.382606128 | None | None | N |
| I/V | 0.0954 | likely_benign | 0.0948 | benign | -1.139 | Destabilizing | 0.005 | N | 0.29 | neutral | N | 0.396125394 | None | None | N |
| I/W | 0.9806 | likely_pathogenic | 0.9831 | pathogenic | -1.275 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9032 | likely_pathogenic | 0.9174 | pathogenic | -1.039 | Destabilizing | 0.974 | D | 0.573 | 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.