Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27913 | 83962;83963;83964 | chr2:178562395;178562394;178562393 | chr2:179427122;179427121;179427120 |
| N2AB | 26272 | 79039;79040;79041 | chr2:178562395;178562394;178562393 | chr2:179427122;179427121;179427120 |
| N2A | 25345 | 76258;76259;76260 | chr2:178562395;178562394;178562393 | chr2:179427122;179427121;179427120 |
| N2B | 18848 | 56767;56768;56769 | chr2:178562395;178562394;178562393 | chr2:179427122;179427121;179427120 |
| Novex-1 | 18973 | 57142;57143;57144 | chr2:178562395;178562394;178562393 | chr2:179427122;179427121;179427120 |
| Novex-2 | 19040 | 57343;57344;57345 | chr2:178562395;178562394;178562393 | chr2:179427122;179427121;179427120 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 1.0 | N | 0.829 | 0.507 | 0.833376837834 | gnomAD-4.0.0 | 1.59663E-06 | None | None | None | None | N | None | 0 | 2.30001E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/S | rs1296750287  |
-0.749 | 1.0 | N | 0.739 | 0.493 | 0.769874456748 | gnomAD-4.0.0 | 6.85371E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16814E-05 | 0 |
| C/Y | rs1296750287 |
None | 1.0 | N | 0.832 | 0.377 | 0.820914700047 | gnomAD-4.0.0 | 6.85371E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00137E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.3459 | ambiguous | 0.3817 | ambiguous | -1.286 | Destabilizing | 0.998 | D | 0.517 | neutral | None | None | None | None | N |
| C/D | 0.9212 | likely_pathogenic | 0.9421 | pathogenic | 0.262 | Stabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| C/E | 0.94 | likely_pathogenic | 0.9579 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| C/F | 0.3108 | likely_benign | 0.378 | ambiguous | -0.922 | Destabilizing | 1.0 | D | 0.828 | deleterious | N | 0.473149076 | None | None | N |
| C/G | 0.2548 | likely_benign | 0.3171 | benign | -1.526 | Destabilizing | 1.0 | D | 0.794 | deleterious | N | 0.469594358 | None | None | N |
| C/H | 0.7419 | likely_pathogenic | 0.8065 | pathogenic | -1.52 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| C/I | 0.4505 | ambiguous | 0.4819 | ambiguous | -0.711 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| C/K | 0.9218 | likely_pathogenic | 0.942 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| C/L | 0.5541 | ambiguous | 0.5879 | pathogenic | -0.711 | Destabilizing | 1.0 | D | 0.538 | neutral | None | None | None | None | N |
| C/M | 0.6848 | likely_pathogenic | 0.7087 | pathogenic | -0.115 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| C/N | 0.7606 | likely_pathogenic | 0.8117 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| C/P | 0.9435 | likely_pathogenic | 0.9552 | pathogenic | -0.876 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| C/Q | 0.824 | likely_pathogenic | 0.86 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| C/R | 0.6896 | likely_pathogenic | 0.7509 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.829 | deleterious | N | 0.495305482 | None | None | N |
| C/S | 0.3309 | likely_benign | 0.3988 | ambiguous | -0.778 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.51705465 | None | None | N |
| C/T | 0.5148 | ambiguous | 0.5688 | pathogenic | -0.572 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| C/V | 0.3105 | likely_benign | 0.3326 | benign | -0.876 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| C/W | 0.7247 | likely_pathogenic | 0.8022 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.811 | deleterious | N | 0.504841816 | None | None | N |
| C/Y | 0.4801 | ambiguous | 0.5697 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.832 | deleterious | N | 0.519556237 | 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.