Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17227 | 51904;51905;51906 | chr2:178609744;178609743;178609742 | chr2:179474471;179474470;179474469 |
| N2AB | 15586 | 46981;46982;46983 | chr2:178609744;178609743;178609742 | chr2:179474471;179474470;179474469 |
| N2A | 14659 | 44200;44201;44202 | chr2:178609744;178609743;178609742 | chr2:179474471;179474470;179474469 |
| N2B | 8162 | 24709;24710;24711 | chr2:178609744;178609743;178609742 | chr2:179474471;179474470;179474469 |
| Novex-1 | 8287 | 25084;25085;25086 | chr2:178609744;178609743;178609742 | chr2:179474471;179474470;179474469 |
| Novex-2 | 8354 | 25285;25286;25287 | chr2:178609744;178609743;178609742 | chr2:179474471;179474470;179474469 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs904223315  |
-0.116 | 1.0 | N | 0.691 | 0.289 | 0.455265801863 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 8.71E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/T | rs904223315 |
-0.116 | 1.0 | N | 0.691 | 0.289 | 0.455265801863 | gnomAD-4.0.0 | 1.09575E-05 | None | None | None | None | I | None | 2.99455E-05 | 8.94775E-05 | None | 0 | 0 | None | 0 | 0 | 7.20154E-06 | 1.16122E-05 | 3.31664E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.679 | likely_pathogenic | 0.6631 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| A/D | 0.6361 | likely_pathogenic | 0.5223 | ambiguous | -0.47 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.488524041 | None | None | I |
| A/E | 0.4969 | ambiguous | 0.4009 | ambiguous | -0.638 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| A/F | 0.5135 | ambiguous | 0.4817 | ambiguous | -0.887 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| A/G | 0.285 | likely_benign | 0.2659 | benign | -0.11 | Destabilizing | 1.0 | D | 0.512 | neutral | N | 0.507624303 | None | None | I |
| A/H | 0.6994 | likely_pathogenic | 0.6373 | pathogenic | -0.17 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| A/I | 0.2744 | likely_benign | 0.2645 | benign | -0.263 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| A/K | 0.7873 | likely_pathogenic | 0.6832 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| A/L | 0.2138 | likely_benign | 0.2045 | benign | -0.263 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| A/M | 0.2788 | likely_benign | 0.2694 | benign | -0.219 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| A/N | 0.4138 | ambiguous | 0.3863 | ambiguous | -0.014 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| A/P | 0.4802 | ambiguous | 0.4882 | ambiguous | -0.178 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.485870525 | None | None | I |
| A/Q | 0.511 | ambiguous | 0.4685 | ambiguous | -0.339 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| A/R | 0.7263 | likely_pathogenic | 0.6125 | pathogenic | 0.138 | Stabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| A/S | 0.1402 | likely_benign | 0.1366 | benign | -0.178 | Destabilizing | 1.0 | D | 0.53 | neutral | N | 0.475864175 | None | None | I |
| A/T | 0.1454 | likely_benign | 0.1254 | benign | -0.275 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.521135105 | None | None | I |
| A/V | 0.158 | likely_benign | 0.1459 | benign | -0.178 | Destabilizing | 1.0 | D | 0.613 | neutral | N | 0.455643618 | None | None | I |
| A/W | 0.8955 | likely_pathogenic | 0.8665 | pathogenic | -1.005 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| A/Y | 0.679 | likely_pathogenic | 0.6302 | pathogenic | -0.632 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | 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.