Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14086 | 42481;42482;42483 | chr2:178634525;178634524;178634523 | chr2:179499252;179499251;179499250 |
| N2AB | 12445 | 37558;37559;37560 | chr2:178634525;178634524;178634523 | chr2:179499252;179499251;179499250 |
| N2A | 11518 | 34777;34778;34779 | chr2:178634525;178634524;178634523 | chr2:179499252;179499251;179499250 |
| N2B | 5021 | 15286;15287;15288 | chr2:178634525;178634524;178634523 | chr2:179499252;179499251;179499250 |
| Novex-1 | 5146 | 15661;15662;15663 | chr2:178634525;178634524;178634523 | chr2:179499252;179499251;179499250 |
| Novex-2 | 5213 | 15862;15863;15864 | chr2:178634525;178634524;178634523 | chr2:179499252;179499251;179499250 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/T | rs777451130  |
-0.431 | 0.784 | N | 0.575 | 0.136 | 0.139678290688 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/T | rs777451130 |
-0.431 | 0.784 | N | 0.575 | 0.136 | 0.139678290688 | gnomAD-4.0.0 | 2.39534E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.96883E-05 | 0 | 3.31477E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1219 | likely_benign | 0.1216 | benign | -0.859 | Destabilizing | 0.425 | N | 0.464 | neutral | N | 0.436442528 | None | None | N |
| S/C | 0.1314 | likely_benign | 0.1265 | benign | -0.613 | Destabilizing | 0.993 | D | 0.641 | neutral | N | 0.453440536 | None | None | N |
| S/D | 0.8132 | likely_pathogenic | 0.8058 | pathogenic | -0.743 | Destabilizing | 0.936 | D | 0.641 | neutral | None | None | None | None | N |
| S/E | 0.6758 | likely_pathogenic | 0.675 | pathogenic | -0.619 | Destabilizing | 0.828 | D | 0.618 | neutral | None | None | None | None | N |
| S/F | 0.2904 | likely_benign | 0.3143 | benign | -0.922 | Destabilizing | 0.006 | N | 0.477 | neutral | N | 0.374002455 | None | None | N |
| S/G | 0.1796 | likely_benign | 0.1734 | benign | -1.207 | Destabilizing | 0.828 | D | 0.605 | neutral | None | None | None | None | N |
| S/H | 0.3713 | ambiguous | 0.3584 | ambiguous | -1.635 | Destabilizing | 0.893 | D | 0.66 | neutral | None | None | None | None | N |
| S/I | 0.3482 | ambiguous | 0.3381 | benign | -0.006 | Destabilizing | 0.543 | D | 0.666 | neutral | None | None | None | None | N |
| S/K | 0.658 | likely_pathogenic | 0.636 | pathogenic | -0.276 | Destabilizing | 0.828 | D | 0.611 | neutral | None | None | None | None | N |
| S/L | 0.1243 | likely_benign | 0.1333 | benign | -0.006 | Destabilizing | 0.003 | N | 0.469 | neutral | None | None | None | None | N |
| S/M | 0.2276 | likely_benign | 0.2217 | benign | 0.069 | Stabilizing | 0.893 | D | 0.673 | neutral | None | None | None | None | N |
| S/N | 0.2813 | likely_benign | 0.2689 | benign | -0.714 | Destabilizing | 0.828 | D | 0.627 | neutral | None | None | None | None | N |
| S/P | 0.9881 | likely_pathogenic | 0.9889 | pathogenic | -0.256 | Destabilizing | 0.975 | D | 0.673 | neutral | N | 0.480711742 | None | None | N |
| S/Q | 0.4976 | ambiguous | 0.4812 | ambiguous | -0.634 | Destabilizing | 0.981 | D | 0.668 | neutral | None | None | None | None | N |
| S/R | 0.5648 | likely_pathogenic | 0.5495 | ambiguous | -0.513 | Destabilizing | 0.944 | D | 0.684 | prob.neutral | None | None | None | None | N |
| S/T | 0.1208 | likely_benign | 0.1142 | benign | -0.549 | Destabilizing | 0.784 | D | 0.575 | neutral | N | 0.443697782 | None | None | N |
| S/V | 0.3482 | ambiguous | 0.3335 | benign | -0.256 | Destabilizing | 0.329 | N | 0.655 | neutral | None | None | None | None | N |
| S/W | 0.3332 | likely_benign | 0.3529 | ambiguous | -1.01 | Destabilizing | 0.985 | D | 0.675 | neutral | None | None | None | None | N |
| S/Y | 0.1914 | likely_benign | 0.2058 | benign | -0.624 | Destabilizing | 0.002 | N | 0.465 | neutral | N | 0.376319412 | 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.