Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3039 | 9340;9341;9342 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
| N2AB | 3039 | 9340;9341;9342 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
| N2A | 3039 | 9340;9341;9342 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
| N2B | 2993 | 9202;9203;9204 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
| Novex-1 | 2993 | 9202;9203;9204 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
| Novex-2 | 2993 | 9202;9203;9204 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
| Novex-3 | 3039 | 9340;9341;9342 | chr2:178768721;178768720;178768719 | chr2:179633448;179633447;179633446 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs774523194  |
-0.199 | 0.896 | N | 0.725 | 0.161 | 0.379881503574 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | N | None | 0 | 1.15734E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.63185E-04 |
| T/I | rs774523194 |
-0.199 | 0.896 | N | 0.725 | 0.161 | 0.379881503574 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 2.62055E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs774523194 |
-0.199 | 0.896 | N | 0.725 | 0.161 | 0.379881503574 | gnomAD-4.0.0 | 1.28069E-05 | None | None | None | None | N | None | 0 | 1.35607E-04 | None | 0 | 0 | None | 0 | 0 | 2.39172E-06 | 0 | 2.84204E-05 |
| T/N | None | -0.746 | 0.379 | D | 0.679 | 0.186 | 0.31077124679 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| T/S | rs774523194 |
-1.139 | 0.007 | N | 0.293 | 0.154 | 0.107399877778 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs774523194 |
-1.139 | 0.007 | N | 0.293 | 0.154 | 0.107399877778 | gnomAD-4.0.0 | 1.59066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1309 | likely_benign | 0.141 | benign | -1.512 | Destabilizing | 0.201 | N | 0.495 | neutral | N | 0.462357567 | None | None | N |
| T/C | 0.4552 | ambiguous | 0.5427 | ambiguous | -0.966 | Destabilizing | 0.992 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/D | 0.7742 | likely_pathogenic | 0.7974 | pathogenic | -1.33 | Destabilizing | 0.617 | D | 0.702 | prob.neutral | None | None | None | None | N |
| T/E | 0.5457 | ambiguous | 0.532 | ambiguous | -1.093 | Destabilizing | 0.25 | N | 0.659 | neutral | None | None | None | None | N |
| T/F | 0.4949 | ambiguous | 0.5167 | ambiguous | -1.232 | Destabilizing | 0.92 | D | 0.704 | prob.neutral | None | None | None | None | N |
| T/G | 0.5323 | ambiguous | 0.5794 | pathogenic | -1.919 | Destabilizing | 0.447 | N | 0.697 | prob.neutral | None | None | None | None | N |
| T/H | 0.3725 | ambiguous | 0.4084 | ambiguous | -1.783 | Destabilizing | 0.92 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/I | 0.2418 | likely_benign | 0.2405 | benign | -0.418 | Destabilizing | 0.896 | D | 0.725 | prob.delet. | N | 0.450349576 | None | None | N |
| T/K | 0.3427 | ambiguous | 0.3496 | ambiguous | -0.142 | Destabilizing | 0.021 | N | 0.446 | neutral | None | None | None | None | N |
| T/L | 0.2012 | likely_benign | 0.1997 | benign | -0.418 | Destabilizing | 0.617 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/M | 0.1112 | likely_benign | 0.1066 | benign | -0.549 | Destabilizing | 0.972 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/N | 0.2892 | likely_benign | 0.3154 | benign | -0.869 | Destabilizing | 0.379 | N | 0.679 | prob.neutral | D | 0.523547233 | None | None | N |
| T/P | 0.9515 | likely_pathogenic | 0.9477 | pathogenic | -0.756 | Destabilizing | 0.712 | D | 0.729 | prob.delet. | D | 0.523740872 | None | None | N |
| T/Q | 0.2948 | likely_benign | 0.3037 | benign | -0.639 | Destabilizing | 0.059 | N | 0.431 | neutral | None | None | None | None | N |
| T/R | 0.2817 | likely_benign | 0.2784 | benign | -0.418 | Destabilizing | 0.447 | N | 0.703 | prob.neutral | None | None | None | None | N |
| T/S | 0.1334 | likely_benign | 0.1484 | benign | -1.228 | Destabilizing | 0.007 | N | 0.293 | neutral | N | 0.417653688 | None | None | N |
| T/V | 0.18 | likely_benign | 0.1755 | benign | -0.756 | Destabilizing | 0.617 | D | 0.671 | neutral | None | None | None | None | N |
| T/W | 0.8629 | likely_pathogenic | 0.8613 | pathogenic | -1.248 | Destabilizing | 0.992 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/Y | 0.5254 | ambiguous | 0.5643 | pathogenic | -0.89 | Destabilizing | 0.972 | D | 0.694 | prob.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.