Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26725 | 80398;80399;80400 | chr2:178565959;178565958;178565957 | chr2:179430686;179430685;179430684 |
| N2AB | 25084 | 75475;75476;75477 | chr2:178565959;178565958;178565957 | chr2:179430686;179430685;179430684 |
| N2A | 24157 | 72694;72695;72696 | chr2:178565959;178565958;178565957 | chr2:179430686;179430685;179430684 |
| N2B | 17660 | 53203;53204;53205 | chr2:178565959;178565958;178565957 | chr2:179430686;179430685;179430684 |
| Novex-1 | 17785 | 53578;53579;53580 | chr2:178565959;178565958;178565957 | chr2:179430686;179430685;179430684 |
| Novex-2 | 17852 | 53779;53780;53781 | chr2:178565959;178565958;178565957 | chr2:179430686;179430685;179430684 |
| 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/L | rs772603198  |
0.148 | 1.0 | N | 0.643 | 0.486 | 0.356484672536 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/L | rs772603198 |
0.148 | 1.0 | N | 0.643 | 0.486 | 0.356484672536 | gnomAD-4.0.0 | 1.59166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85907E-06 | 0 | 0 |
| S/P | None | None | 0.999 | N | 0.687 | 0.555 | 0.339074221408 | gnomAD-4.0.0 | 2.05284E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69866E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0817 | likely_benign | 0.0819 | benign | -0.574 | Destabilizing | 0.936 | D | 0.523 | neutral | N | 0.400115623 | None | None | N |
| S/C | 0.2346 | likely_benign | 0.2572 | benign | -0.354 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| S/D | 0.8807 | likely_pathogenic | 0.9156 | pathogenic | 0.37 | Stabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| S/E | 0.8862 | likely_pathogenic | 0.9201 | pathogenic | 0.364 | Stabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| S/F | 0.624 | likely_pathogenic | 0.6604 | pathogenic | -0.74 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/G | 0.1609 | likely_benign | 0.1708 | benign | -0.812 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| S/H | 0.8144 | likely_pathogenic | 0.8483 | pathogenic | -1.11 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| S/I | 0.4002 | ambiguous | 0.4562 | ambiguous | -0.053 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/K | 0.958 | likely_pathogenic | 0.9747 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| S/L | 0.2394 | likely_benign | 0.2675 | benign | -0.053 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.495546014 | None | None | N |
| S/M | 0.3301 | likely_benign | 0.3672 | ambiguous | -0.003 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/N | 0.4055 | ambiguous | 0.4489 | ambiguous | -0.344 | Destabilizing | 0.987 | D | 0.644 | neutral | None | None | None | None | N |
| S/P | 0.7327 | likely_pathogenic | 0.7329 | pathogenic | -0.193 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | N | 0.487793322 | None | None | N |
| S/Q | 0.8309 | likely_pathogenic | 0.8666 | pathogenic | -0.436 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| S/R | 0.95 | likely_pathogenic | 0.9668 | pathogenic | -0.351 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| S/T | 0.1552 | likely_benign | 0.172 | benign | -0.431 | Destabilizing | 0.982 | D | 0.558 | neutral | N | 0.443847757 | None | None | N |
| S/V | 0.3501 | ambiguous | 0.4 | ambiguous | -0.193 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| S/W | 0.7815 | likely_pathogenic | 0.8149 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| S/Y | 0.5343 | ambiguous | 0.5888 | pathogenic | -0.455 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | 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.