Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34343 | 103252;103253;103254 | chr2:178533588;178533587;178533586 | chr2:179398315;179398314;179398313 |
| N2AB | 32702 | 98329;98330;98331 | chr2:178533588;178533587;178533586 | chr2:179398315;179398314;179398313 |
| N2A | 31775 | 95548;95549;95550 | chr2:178533588;178533587;178533586 | chr2:179398315;179398314;179398313 |
| N2B | 25278 | 76057;76058;76059 | chr2:178533588;178533587;178533586 | chr2:179398315;179398314;179398313 |
| Novex-1 | 25403 | 76432;76433;76434 | chr2:178533588;178533587;178533586 | chr2:179398315;179398314;179398313 |
| Novex-2 | 25470 | 76633;76634;76635 | chr2:178533588;178533587;178533586 | chr2:179398315;179398314;179398313 |
| 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/R | rs375852057  |
-0.195 | 0.991 | D | 0.688 | 0.507 | 0.53046153047 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| S/R | rs375852057 |
-0.195 | 0.991 | D | 0.688 | 0.507 | 0.53046153047 | gnomAD-4.0.0 | 2.40066E-06 | None | None | None | None | N | None | 1.26695E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1303 | likely_benign | 0.1188 | benign | -0.442 | Destabilizing | 0.893 | D | 0.407 | neutral | None | None | None | None | N |
| S/C | 0.1764 | likely_benign | 0.169 | benign | -0.33 | Destabilizing | 0.999 | D | 0.657 | neutral | N | 0.517309845 | None | None | N |
| S/D | 0.7057 | likely_pathogenic | 0.6382 | pathogenic | 0.249 | Stabilizing | 0.976 | D | 0.448 | neutral | None | None | None | None | N |
| S/E | 0.6963 | likely_pathogenic | 0.648 | pathogenic | 0.216 | Stabilizing | 0.953 | D | 0.443 | neutral | None | None | None | None | N |
| S/F | 0.335 | likely_benign | 0.2755 | benign | -0.77 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/G | 0.2395 | likely_benign | 0.2034 | benign | -0.64 | Destabilizing | 0.969 | D | 0.439 | neutral | D | 0.523132742 | None | None | N |
| S/H | 0.4554 | ambiguous | 0.422 | ambiguous | -1.01 | Destabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| S/I | 0.2489 | likely_benign | 0.2005 | benign | -0.038 | Destabilizing | 0.991 | D | 0.699 | prob.neutral | D | 0.535099772 | None | None | N |
| S/K | 0.8172 | likely_pathogenic | 0.78 | pathogenic | -0.508 | Destabilizing | 0.953 | D | 0.452 | neutral | None | None | None | None | N |
| S/L | 0.2034 | likely_benign | 0.1651 | benign | -0.038 | Destabilizing | 0.986 | D | 0.644 | neutral | None | None | None | None | N |
| S/M | 0.314 | likely_benign | 0.2706 | benign | -0.022 | Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | N |
| S/N | 0.2616 | likely_benign | 0.2124 | benign | -0.356 | Destabilizing | 0.969 | D | 0.468 | neutral | D | 0.528384443 | None | None | N |
| S/P | 0.9806 | likely_pathogenic | 0.9709 | pathogenic | -0.139 | Destabilizing | 0.06 | N | 0.362 | neutral | None | None | None | None | N |
| S/Q | 0.6404 | likely_pathogenic | 0.5981 | pathogenic | -0.47 | Destabilizing | 0.993 | D | 0.561 | neutral | None | None | None | None | N |
| S/R | 0.69 | likely_pathogenic | 0.643 | pathogenic | -0.365 | Destabilizing | 0.991 | D | 0.688 | prob.neutral | D | 0.532251468 | None | None | N |
| S/T | 0.0963 | likely_benign | 0.0873 | benign | -0.405 | Destabilizing | 0.969 | D | 0.418 | neutral | N | 0.496903956 | None | None | N |
| S/V | 0.2769 | likely_benign | 0.2319 | benign | -0.139 | Destabilizing | 0.993 | D | 0.627 | neutral | None | None | None | None | N |
| S/W | 0.5786 | likely_pathogenic | 0.5258 | ambiguous | -0.809 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| S/Y | 0.3094 | likely_benign | 0.268 | benign | -0.517 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | 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.