Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2469 | 7630;7631;7632 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
| N2AB | 2469 | 7630;7631;7632 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
| N2A | 2469 | 7630;7631;7632 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
| N2B | 2423 | 7492;7493;7494 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
| Novex-1 | 2423 | 7492;7493;7494 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
| Novex-2 | 2423 | 7492;7493;7494 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
| Novex-3 | 2469 | 7630;7631;7632 | chr2:178773651;178773650;178773649 | chr2:179638378;179638377;179638376 |
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/A | None | None | 0.997 | D | 0.364 | 0.386 | 0.399596177874 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/L | rs2091848374  |
None | 1.0 | D | 0.62 | 0.513 | 0.848577320525 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| S/P | rs1483612704 |
None | 1.0 | D | 0.686 | 0.706 | 0.537777371803 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/P | rs1483612704 |
None | 1.0 | D | 0.686 | 0.706 | 0.537777371803 | gnomAD-4.0.0 | 6.08959E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.22951E-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 | 0.2447 | likely_benign | 0.2425 | benign | -0.468 | Destabilizing | 0.997 | D | 0.364 | neutral | D | 0.553201687 | None | None | N |
| S/C | 0.4947 | ambiguous | 0.4815 | ambiguous | -0.424 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| S/D | 0.8561 | likely_pathogenic | 0.8493 | pathogenic | 0.039 | Stabilizing | 0.999 | D | 0.596 | neutral | None | None | None | None | N |
| S/E | 0.967 | likely_pathogenic | 0.9704 | pathogenic | 0.019 | Stabilizing | 0.999 | D | 0.573 | neutral | None | None | None | None | N |
| S/F | 0.8747 | likely_pathogenic | 0.8822 | pathogenic | -0.667 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| S/G | 0.307 | likely_benign | 0.299 | benign | -0.698 | Destabilizing | 0.999 | D | 0.438 | neutral | None | None | None | None | N |
| S/H | 0.9132 | likely_pathogenic | 0.9164 | pathogenic | -1.178 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| S/I | 0.7831 | likely_pathogenic | 0.7886 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| S/K | 0.9896 | likely_pathogenic | 0.9905 | pathogenic | -0.679 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| S/L | 0.4401 | ambiguous | 0.4545 | ambiguous | 0.025 | Stabilizing | 1.0 | D | 0.62 | neutral | D | 0.666291905 | None | None | N |
| S/M | 0.6456 | likely_pathogenic | 0.6527 | pathogenic | 0.105 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/N | 0.4164 | ambiguous | 0.4068 | ambiguous | -0.576 | Destabilizing | 0.999 | D | 0.552 | neutral | None | None | None | None | N |
| S/P | 0.9507 | likely_pathogenic | 0.9589 | pathogenic | -0.105 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | D | 0.553741393 | None | None | N |
| S/Q | 0.9537 | likely_pathogenic | 0.9589 | pathogenic | -0.693 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| S/R | 0.9828 | likely_pathogenic | 0.9845 | pathogenic | -0.58 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/T | 0.1479 | likely_benign | 0.1508 | benign | -0.594 | Destabilizing | 0.999 | D | 0.423 | neutral | N | 0.50768377 | None | None | N |
| S/V | 0.7322 | likely_pathogenic | 0.7418 | pathogenic | -0.105 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/W | 0.925 | likely_pathogenic | 0.9315 | pathogenic | -0.69 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| S/Y | 0.8189 | likely_pathogenic | 0.8307 | pathogenic | -0.415 | Destabilizing | 1.0 | D | 0.697 | 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.