Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34185 | 102778;102779;102780 | chr2:178534062;178534061;178534060 | chr2:179398789;179398788;179398787 |
| N2AB | 32544 | 97855;97856;97857 | chr2:178534062;178534061;178534060 | chr2:179398789;179398788;179398787 |
| N2A | 31617 | 95074;95075;95076 | chr2:178534062;178534061;178534060 | chr2:179398789;179398788;179398787 |
| N2B | 25120 | 75583;75584;75585 | chr2:178534062;178534061;178534060 | chr2:179398789;179398788;179398787 |
| Novex-1 | 25245 | 75958;75959;75960 | chr2:178534062;178534061;178534060 | chr2:179398789;179398788;179398787 |
| Novex-2 | 25312 | 76159;76160;76161 | chr2:178534062;178534061;178534060 | chr2:179398789;179398788;179398787 |
| 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/L | None | None | 0.889 | D | 0.339 | 0.329 | 0.48095081912 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92456E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | None | None | 0.889 | D | 0.339 | 0.329 | 0.48095081912 | gnomAD-4.0.0 | 6.56944E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.92456E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1280013764  |
-2.115 | 0.994 | D | 0.618 | 0.607 | 0.758643912819 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| I/T | rs1280013764 |
-2.115 | 0.994 | D | 0.618 | 0.607 | 0.758643912819 | gnomAD-4.0.0 | 1.591E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8577E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8058 | likely_pathogenic | 0.818 | pathogenic | -2.307 | Highly Destabilizing | 0.992 | D | 0.507 | neutral | None | None | None | None | N |
| I/C | 0.8957 | likely_pathogenic | 0.9221 | pathogenic | -1.382 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/D | 0.9698 | likely_pathogenic | 0.971 | pathogenic | -2.177 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| I/E | 0.9031 | likely_pathogenic | 0.9038 | pathogenic | -2.087 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/F | 0.3602 | ambiguous | 0.3434 | ambiguous | -1.58 | Destabilizing | 0.998 | D | 0.567 | neutral | N | 0.518207522 | None | None | N |
| I/G | 0.9545 | likely_pathogenic | 0.9584 | pathogenic | -2.74 | Highly Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| I/H | 0.8974 | likely_pathogenic | 0.8992 | pathogenic | -2.057 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/K | 0.7443 | likely_pathogenic | 0.7519 | pathogenic | -1.696 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | N |
| I/L | 0.2535 | likely_benign | 0.2626 | benign | -1.12 | Destabilizing | 0.889 | D | 0.339 | neutral | D | 0.523111909 | None | None | N |
| I/M | 0.1102 | likely_benign | 0.1062 | benign | -0.799 | Destabilizing | 0.889 | D | 0.374 | neutral | N | 0.515628577 | None | None | N |
| I/N | 0.7124 | likely_pathogenic | 0.7099 | pathogenic | -1.642 | Destabilizing | 0.999 | D | 0.817 | deleterious | N | 0.518425935 | None | None | N |
| I/P | 0.9853 | likely_pathogenic | 0.9862 | pathogenic | -1.49 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/Q | 0.8152 | likely_pathogenic | 0.8042 | pathogenic | -1.726 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| I/R | 0.7207 | likely_pathogenic | 0.7261 | pathogenic | -1.155 | Destabilizing | 0.999 | D | 0.812 | deleterious | None | None | None | None | N |
| I/S | 0.8095 | likely_pathogenic | 0.8126 | pathogenic | -2.287 | Highly Destabilizing | 0.998 | D | 0.669 | neutral | N | 0.491167421 | None | None | N |
| I/T | 0.7312 | likely_pathogenic | 0.7597 | pathogenic | -2.071 | Highly Destabilizing | 0.994 | D | 0.618 | neutral | D | 0.533638334 | None | None | N |
| I/V | 0.1665 | likely_benign | 0.1917 | benign | -1.49 | Destabilizing | 0.889 | D | 0.395 | neutral | N | 0.498981469 | None | None | N |
| I/W | 0.9329 | likely_pathogenic | 0.9279 | pathogenic | -1.809 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/Y | 0.7485 | likely_pathogenic | 0.7323 | pathogenic | -1.574 | Destabilizing | 1.0 | D | 0.68 | 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.