Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31222 | 93889;93890;93891 | chr2:178547962;178547961;178547960 | chr2:179412689;179412688;179412687 |
| N2AB | 29581 | 88966;88967;88968 | chr2:178547962;178547961;178547960 | chr2:179412689;179412688;179412687 |
| N2A | 28654 | 86185;86186;86187 | chr2:178547962;178547961;178547960 | chr2:179412689;179412688;179412687 |
| N2B | 22157 | 66694;66695;66696 | chr2:178547962;178547961;178547960 | chr2:179412689;179412688;179412687 |
| Novex-1 | 22282 | 67069;67070;67071 | chr2:178547962;178547961;178547960 | chr2:179412689;179412688;179412687 |
| Novex-2 | 22349 | 67270;67271;67272 | chr2:178547962;178547961;178547960 | chr2:179412689;179412688;179412687 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs760845662  |
-0.394 | 0.009 | N | 0.24 | 0.13 | 0.141422826196 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| N/H | rs760845662 |
-0.394 | 0.009 | N | 0.24 | 0.13 | 0.141422826196 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/H | rs760845662 |
-0.394 | 0.009 | N | 0.24 | 0.13 | 0.141422826196 | gnomAD-4.0.0 | 3.71841E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08587E-06 | 0 | 0 |
| N/S | rs1559164640 |
None | 0.334 | N | 0.404 | 0.152 | 0.12205267543 | gnomAD-4.0.0 | 3.42129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49751E-06 | 0 | 0 |
| N/Y | None | None | 0.681 | N | 0.449 | 0.257 | 0.485348376517 | gnomAD-4.0.0 | 6.8426E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99514E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.255 | likely_benign | 0.208 | benign | -0.063 | Destabilizing | 0.4 | N | 0.411 | neutral | None | None | None | None | I |
| N/C | 0.4037 | ambiguous | 0.3166 | benign | 0.126 | Stabilizing | 0.992 | D | 0.433 | neutral | None | None | None | None | I |
| N/D | 0.1139 | likely_benign | 0.1045 | benign | 0.056 | Stabilizing | 0.549 | D | 0.369 | neutral | N | 0.444221477 | None | None | I |
| N/E | 0.3315 | likely_benign | 0.2561 | benign | -0.008 | Destabilizing | 0.4 | N | 0.37 | neutral | None | None | None | None | I |
| N/F | 0.7514 | likely_pathogenic | 0.6743 | pathogenic | -0.681 | Destabilizing | 0.85 | D | 0.446 | neutral | None | None | None | None | I |
| N/G | 0.1953 | likely_benign | 0.1756 | benign | -0.15 | Destabilizing | 0.4 | N | 0.373 | neutral | None | None | None | None | I |
| N/H | 0.105 | likely_benign | 0.0808 | benign | -0.187 | Destabilizing | 0.009 | N | 0.24 | neutral | N | 0.463847388 | None | None | I |
| N/I | 0.5756 | likely_pathogenic | 0.4869 | ambiguous | 0.065 | Stabilizing | 0.896 | D | 0.451 | neutral | N | 0.463847388 | None | None | I |
| N/K | 0.2328 | likely_benign | 0.1465 | benign | 0.086 | Stabilizing | 0.007 | N | 0.173 | neutral | N | 0.393331297 | None | None | I |
| N/L | 0.3937 | ambiguous | 0.3241 | benign | 0.065 | Stabilizing | 0.617 | D | 0.425 | neutral | None | None | None | None | I |
| N/M | 0.5177 | ambiguous | 0.4367 | ambiguous | 0.097 | Stabilizing | 0.972 | D | 0.418 | neutral | None | None | None | None | I |
| N/P | 0.6225 | likely_pathogenic | 0.5929 | pathogenic | 0.045 | Stabilizing | 0.972 | D | 0.436 | neutral | None | None | None | None | I |
| N/Q | 0.2507 | likely_benign | 0.1791 | benign | -0.289 | Destabilizing | 0.617 | D | 0.365 | neutral | None | None | None | None | I |
| N/R | 0.2552 | likely_benign | 0.1605 | benign | 0.141 | Stabilizing | 0.002 | N | 0.165 | neutral | None | None | None | None | I |
| N/S | 0.0772 | likely_benign | 0.0744 | benign | -0.052 | Destabilizing | 0.334 | N | 0.404 | neutral | N | 0.414071929 | None | None | I |
| N/T | 0.1964 | likely_benign | 0.1622 | benign | -0.008 | Destabilizing | 0.712 | D | 0.339 | neutral | N | 0.444741552 | None | None | I |
| N/V | 0.4746 | ambiguous | 0.3994 | ambiguous | 0.045 | Stabilizing | 0.766 | D | 0.435 | neutral | None | None | None | None | I |
| N/W | 0.7837 | likely_pathogenic | 0.6924 | pathogenic | -0.832 | Destabilizing | 0.992 | D | 0.479 | neutral | None | None | None | None | I |
| N/Y | 0.2587 | likely_benign | 0.1968 | benign | -0.5 | Destabilizing | 0.681 | D | 0.449 | neutral | N | 0.464367463 | 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.