Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15832 | 47719;47720;47721 | chr2:178617857;178617856;178617855 | chr2:179482584;179482583;179482582 |
| N2AB | 14191 | 42796;42797;42798 | chr2:178617857;178617856;178617855 | chr2:179482584;179482583;179482582 |
| N2A | 13264 | 40015;40016;40017 | chr2:178617857;178617856;178617855 | chr2:179482584;179482583;179482582 |
| N2B | 6767 | 20524;20525;20526 | chr2:178617857;178617856;178617855 | chr2:179482584;179482583;179482582 |
| Novex-1 | 6892 | 20899;20900;20901 | chr2:178617857;178617856;178617855 | chr2:179482584;179482583;179482582 |
| Novex-2 | 6959 | 21100;21101;21102 | chr2:178617857;178617856;178617855 | chr2:179482584;179482583;179482582 |
| 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/P | None | None | 1.0 | D | 0.807 | 0.643 | 0.7687812343 | gnomAD-4.0.0 | 1.36935E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79991E-06 | 0 | 0 |
| R/Q | rs376140223  |
-1.154 | 1.0 | D | 0.785 | 0.363 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 1.29433E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.92E-06 | 0 |
| R/Q | rs376140223 |
-1.154 | 1.0 | D | 0.785 | 0.363 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs376140223 |
-1.154 | 1.0 | D | 0.785 | 0.363 | None | gnomAD-4.0.0 | 4.96139E-06 | None | None | None | None | I | None | 2.6743E-05 | 1.66962E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 4.39396E-05 | 1.60344E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9696 | likely_pathogenic | 0.9547 | pathogenic | -1.86 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | I |
| R/C | 0.6173 | likely_pathogenic | 0.5552 | ambiguous | -1.781 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | I |
| R/D | 0.9977 | likely_pathogenic | 0.9966 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| R/E | 0.964 | likely_pathogenic | 0.9469 | pathogenic | -0.821 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | I |
| R/F | 0.9656 | likely_pathogenic | 0.9595 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| R/G | 0.9754 | likely_pathogenic | 0.9651 | pathogenic | -2.161 | Highly Destabilizing | 1.0 | D | 0.732 | prob.delet. | D | 0.781102456 | None | None | I |
| R/H | 0.3832 | ambiguous | 0.3693 | ambiguous | -2.195 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| R/I | 0.9246 | likely_pathogenic | 0.892 | pathogenic | -0.99 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| R/K | 0.645 | likely_pathogenic | 0.575 | pathogenic | -1.309 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | I |
| R/L | 0.8817 | likely_pathogenic | 0.8418 | pathogenic | -0.99 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | D | 0.644198151 | None | None | I |
| R/M | 0.946 | likely_pathogenic | 0.9172 | pathogenic | -1.505 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| R/N | 0.988 | likely_pathogenic | 0.9812 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| R/P | 0.9987 | likely_pathogenic | 0.9982 | pathogenic | -1.269 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.782397844 | None | None | I |
| R/Q | 0.4139 | ambiguous | 0.4876 | ambiguous | -1.051 | Destabilizing | 1.0 | D | 0.785 | deleterious | D | 0.576678272 | None | None | I |
| R/S | 0.9799 | likely_pathogenic | 0.9706 | pathogenic | -1.993 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/T | 0.9689 | likely_pathogenic | 0.9505 | pathogenic | -1.61 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/V | 0.9355 | likely_pathogenic | 0.9095 | pathogenic | -1.269 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | I |
| R/W | 0.7377 | likely_pathogenic | 0.6982 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| R/Y | 0.9303 | likely_pathogenic | 0.9186 | pathogenic | -0.63 | Destabilizing | 1.0 | D | 0.842 | deleterious | 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.