Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33648 | 101167;101168;101169 | chr2:178535673;178535672;178535671 | chr2:179400400;179400399;179400398 |
| N2AB | 32007 | 96244;96245;96246 | chr2:178535673;178535672;178535671 | chr2:179400400;179400399;179400398 |
| N2A | 31080 | 93463;93464;93465 | chr2:178535673;178535672;178535671 | chr2:179400400;179400399;179400398 |
| N2B | 24583 | 73972;73973;73974 | chr2:178535673;178535672;178535671 | chr2:179400400;179400399;179400398 |
| Novex-1 | 24708 | 74347;74348;74349 | chr2:178535673;178535672;178535671 | chr2:179400400;179400399;179400398 |
| Novex-2 | 24775 | 74548;74549;74550 | chr2:178535673;178535672;178535671 | chr2:179400400;179400399;179400398 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | None | None | 1.0 | N | 0.658 | 0.257 | 0.18167952 | gnomAD-4.0.0 | 1.59125E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85825E-06 | 0 | 0 |
| R/T | None | None | 1.0 | N | 0.652 | 0.47 | 0.31590328 | gnomAD-4.0.0 | 3.18251E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71654E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9584 | likely_pathogenic | 0.9245 | pathogenic | -0.021 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| R/C | 0.9008 | likely_pathogenic | 0.778 | pathogenic | -0.282 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| R/D | 0.969 | likely_pathogenic | 0.9391 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/E | 0.9245 | likely_pathogenic | 0.8697 | pathogenic | -0.284 | Destabilizing | 0.996 | D | 0.631 | neutral | None | None | None | None | N |
| R/F | 0.9943 | likely_pathogenic | 0.9884 | pathogenic | -0.377 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/G | 0.8619 | likely_pathogenic | 0.7858 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.609 | neutral | N | 0.43153653 | None | None | N |
| R/H | 0.591 | likely_pathogenic | 0.4529 | ambiguous | -0.575 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| R/I | 0.9858 | likely_pathogenic | 0.9699 | pathogenic | 0.205 | Stabilizing | 0.999 | D | 0.726 | prob.delet. | N | 0.4650013 | None | None | N |
| R/K | 0.4366 | ambiguous | 0.3572 | ambiguous | -0.21 | Destabilizing | 0.971 | D | 0.521 | neutral | N | 0.45867 | None | None | N |
| R/L | 0.947 | likely_pathogenic | 0.9037 | pathogenic | 0.205 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| R/M | 0.9825 | likely_pathogenic | 0.9637 | pathogenic | -0.149 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/N | 0.9602 | likely_pathogenic | 0.9301 | pathogenic | -0.103 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/P | 0.9288 | likely_pathogenic | 0.8451 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| R/Q | 0.5898 | likely_pathogenic | 0.4437 | ambiguous | -0.142 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/S | 0.948 | likely_pathogenic | 0.909 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.658 | neutral | N | 0.41614857 | None | None | N |
| R/T | 0.9587 | likely_pathogenic | 0.9158 | pathogenic | -0.156 | Destabilizing | 1.0 | D | 0.652 | neutral | N | 0.42201853 | None | None | N |
| R/V | 0.9822 | likely_pathogenic | 0.9669 | pathogenic | 0.145 | Stabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| R/W | 0.9351 | likely_pathogenic | 0.8698 | pathogenic | -0.586 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| R/Y | 0.9714 | likely_pathogenic | 0.9459 | pathogenic | -0.2 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | 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.