Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31243 | 93952;93953;93954 | chr2:178547899;178547898;178547897 | chr2:179412626;179412625;179412624 |
| N2AB | 29602 | 89029;89030;89031 | chr2:178547899;178547898;178547897 | chr2:179412626;179412625;179412624 |
| N2A | 28675 | 86248;86249;86250 | chr2:178547899;178547898;178547897 | chr2:179412626;179412625;179412624 |
| N2B | 22178 | 66757;66758;66759 | chr2:178547899;178547898;178547897 | chr2:179412626;179412625;179412624 |
| Novex-1 | 22303 | 67132;67133;67134 | chr2:178547899;178547898;178547897 | chr2:179412626;179412625;179412624 |
| Novex-2 | 22370 | 67333;67334;67335 | chr2:178547899;178547898;178547897 | chr2:179412626;179412625;179412624 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 1.0 | D | 0.776 | 0.702 | 0.703604667544 | gnomAD-4.0.0 | 1.59116E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85793E-06 | 0 | 0 |
| P/S | rs757118302  |
-0.02 | 1.0 | D | 0.763 | 0.68 | 0.62230568396 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 1.16036E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65782E-04 |
| P/S | rs757118302 |
-0.02 | 1.0 | D | 0.763 | 0.68 | 0.62230568396 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs757118302 |
-0.02 | 1.0 | D | 0.763 | 0.68 | 0.62230568396 | gnomAD-4.0.0 | 8.96783E-06 | None | None | None | None | I | None | 0 | 1.01723E-04 | None | 0 | 0 | None | 0 | 2.24215E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.7553 | likely_pathogenic | 0.9075 | pathogenic | -0.411 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.559151712 | None | None | I |
| P/C | 0.9701 | likely_pathogenic | 0.9913 | pathogenic | -0.449 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| P/D | 0.9579 | likely_pathogenic | 0.9807 | pathogenic | -0.397 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| P/E | 0.92 | likely_pathogenic | 0.9714 | pathogenic | -0.533 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| P/F | 0.9804 | likely_pathogenic | 0.9938 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| P/G | 0.9291 | likely_pathogenic | 0.9732 | pathogenic | -0.516 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/H | 0.9037 | likely_pathogenic | 0.9693 | pathogenic | -0.199 | Destabilizing | 1.0 | D | 0.798 | deleterious | D | 0.617582548 | None | None | I |
| P/I | 0.8989 | likely_pathogenic | 0.9548 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| P/K | 0.9278 | likely_pathogenic | 0.9763 | pathogenic | -0.362 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| P/L | 0.7218 | likely_pathogenic | 0.8684 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.776 | deleterious | D | 0.601331022 | None | None | I |
| P/M | 0.9215 | likely_pathogenic | 0.9688 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| P/N | 0.9521 | likely_pathogenic | 0.9792 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| P/Q | 0.882 | likely_pathogenic | 0.9662 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| P/R | 0.8636 | likely_pathogenic | 0.9541 | pathogenic | 0.17 | Stabilizing | 1.0 | D | 0.801 | deleterious | D | 0.617178939 | None | None | I |
| P/S | 0.8922 | likely_pathogenic | 0.9645 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.763 | deleterious | D | 0.558644733 | None | None | I |
| P/T | 0.7751 | likely_pathogenic | 0.9088 | pathogenic | -0.364 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.617178939 | None | None | I |
| P/V | 0.8284 | likely_pathogenic | 0.9238 | pathogenic | -0.298 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| P/W | 0.9881 | likely_pathogenic | 0.9962 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| P/Y | 0.9726 | likely_pathogenic | 0.9907 | pathogenic | -0.569 | Destabilizing | 1.0 | D | 0.823 | 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.