Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18711 | 56356;56357;56358 | chr2:178599770;178599769;178599768 | chr2:179464497;179464496;179464495 |
| N2AB | 17070 | 51433;51434;51435 | chr2:178599770;178599769;178599768 | chr2:179464497;179464496;179464495 |
| N2A | 16143 | 48652;48653;48654 | chr2:178599770;178599769;178599768 | chr2:179464497;179464496;179464495 |
| N2B | 9646 | 29161;29162;29163 | chr2:178599770;178599769;178599768 | chr2:179464497;179464496;179464495 |
| Novex-1 | 9771 | 29536;29537;29538 | chr2:178599770;178599769;178599768 | chr2:179464497;179464496;179464495 |
| Novex-2 | 9838 | 29737;29738;29739 | chr2:178599770;178599769;178599768 | chr2:179464497;179464496;179464495 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs769265168  |
-0.671 | 0.317 | D | 0.537 | 0.365 | 0.798137268733 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| V/G | rs769265168 |
-0.671 | 0.317 | D | 0.537 | 0.365 | 0.798137268733 | gnomAD-4.0.0 | 3.42468E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.5E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3403 | ambiguous | 0.3057 | benign | -0.368 | Destabilizing | 0.027 | N | 0.36 | neutral | N | 0.462274094 | None | None | I |
| V/C | 0.6397 | likely_pathogenic | 0.5027 | ambiguous | -0.853 | Destabilizing | 0.001 | N | 0.291 | neutral | None | None | None | None | I |
| V/D | 0.7133 | likely_pathogenic | 0.6389 | pathogenic | -0.36 | Destabilizing | 0.555 | D | 0.557 | neutral | None | None | None | None | I |
| V/E | 0.526 | ambiguous | 0.4808 | ambiguous | -0.471 | Destabilizing | 0.484 | N | 0.55 | neutral | N | 0.444072336 | None | None | I |
| V/F | 0.2204 | likely_benign | 0.1834 | benign | -0.719 | Destabilizing | 0.38 | N | 0.444 | neutral | None | None | None | None | I |
| V/G | 0.488 | ambiguous | 0.3873 | ambiguous | -0.425 | Destabilizing | 0.317 | N | 0.537 | neutral | D | 0.529384521 | None | None | I |
| V/H | 0.6931 | likely_pathogenic | 0.6128 | pathogenic | 0.011 | Stabilizing | 0.935 | D | 0.554 | neutral | None | None | None | None | I |
| V/I | 0.0794 | likely_benign | 0.0831 | benign | -0.354 | Destabilizing | 0.001 | N | 0.24 | neutral | None | None | None | None | I |
| V/K | 0.4762 | ambiguous | 0.4187 | ambiguous | -0.425 | Destabilizing | 0.38 | N | 0.537 | neutral | None | None | None | None | I |
| V/L | 0.2994 | likely_benign | 0.3067 | benign | -0.354 | Destabilizing | 0.004 | N | 0.221 | neutral | N | 0.452001173 | None | None | I |
| V/M | 0.178 | likely_benign | 0.1826 | benign | -0.636 | Destabilizing | 0.004 | N | 0.22 | neutral | N | 0.518783525 | None | None | I |
| V/N | 0.4803 | ambiguous | 0.4043 | ambiguous | -0.247 | Destabilizing | 0.555 | D | 0.553 | neutral | None | None | None | None | I |
| V/P | 0.9709 | likely_pathogenic | 0.9625 | pathogenic | -0.331 | Destabilizing | 0.791 | D | 0.55 | neutral | None | None | None | None | I |
| V/Q | 0.4383 | ambiguous | 0.3776 | ambiguous | -0.449 | Destabilizing | 0.38 | N | 0.547 | neutral | None | None | None | None | I |
| V/R | 0.4358 | ambiguous | 0.3608 | ambiguous | 0.021 | Stabilizing | 0.38 | N | 0.552 | neutral | None | None | None | None | I |
| V/S | 0.3716 | ambiguous | 0.3039 | benign | -0.56 | Destabilizing | 0.149 | N | 0.543 | neutral | None | None | None | None | I |
| V/T | 0.3293 | likely_benign | 0.3078 | benign | -0.581 | Destabilizing | 0.149 | N | 0.325 | neutral | None | None | None | None | I |
| V/W | 0.8784 | likely_pathogenic | 0.8452 | pathogenic | -0.768 | Destabilizing | 0.935 | D | 0.585 | neutral | None | None | None | None | I |
| V/Y | 0.6122 | likely_pathogenic | 0.5159 | ambiguous | -0.505 | Destabilizing | 0.555 | D | 0.434 | neutral | 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.