Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23619 | 71080;71081;71082 | chr2:178575277;178575276;178575275 | chr2:179440004;179440003;179440002 |
| N2AB | 21978 | 66157;66158;66159 | chr2:178575277;178575276;178575275 | chr2:179440004;179440003;179440002 |
| N2A | 21051 | 63376;63377;63378 | chr2:178575277;178575276;178575275 | chr2:179440004;179440003;179440002 |
| N2B | 14554 | 43885;43886;43887 | chr2:178575277;178575276;178575275 | chr2:179440004;179440003;179440002 |
| Novex-1 | 14679 | 44260;44261;44262 | chr2:178575277;178575276;178575275 | chr2:179440004;179440003;179440002 |
| Novex-2 | 14746 | 44461;44462;44463 | chr2:178575277;178575276;178575275 | chr2:179440004;179440003;179440002 |
| 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/C | None | None | 0.997 | N | 0.713 | 0.419 | 0.384252928164 | gnomAD-4.0.0 | 6.84391E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99588E-07 | 0 | 0 |
| S/G | rs372823646  |
-1.275 | 0.792 | N | 0.599 | 0.234 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 1.40805E-04 |
| S/G | rs372823646 |
-1.275 | 0.792 | N | 0.599 | 0.234 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| S/G | rs372823646 |
-1.275 | 0.792 | N | 0.599 | 0.234 | None | gnomAD-4.0.0 | 4.89694E-05 | None | None | None | None | N | None | 1.33522E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.44277E-05 | 0 | 3.20328E-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 | 0.1906 | likely_benign | 0.1715 | benign | -0.608 | Destabilizing | 0.511 | D | 0.554 | neutral | None | None | None | None | N |
| S/C | 0.2227 | likely_benign | 0.1985 | benign | -0.392 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | N | 0.479251915 | None | None | N |
| S/D | 0.9583 | likely_pathogenic | 0.9585 | pathogenic | -0.406 | Destabilizing | 0.835 | D | 0.71 | prob.delet. | None | None | None | None | N |
| S/E | 0.9716 | likely_pathogenic | 0.9739 | pathogenic | -0.277 | Destabilizing | 0.835 | D | 0.729 | deleterious | None | None | None | None | N |
| S/F | 0.8729 | likely_pathogenic | 0.8568 | pathogenic | -0.427 | Destabilizing | 0.973 | D | 0.785 | deleterious | None | None | None | None | N |
| S/G | 0.2509 | likely_benign | 0.2285 | benign | -0.979 | Destabilizing | 0.792 | D | 0.599 | neutral | N | 0.521036317 | None | None | N |
| S/H | 0.9451 | likely_pathogenic | 0.9439 | pathogenic | -1.309 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | None | None | None | None | N |
| S/I | 0.6337 | likely_pathogenic | 0.5837 | pathogenic | 0.309 | Stabilizing | 0.931 | D | 0.733 | deleterious | N | 0.497658025 | None | None | N |
| S/K | 0.9944 | likely_pathogenic | 0.9951 | pathogenic | -0.291 | Destabilizing | 0.835 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/L | 0.4348 | ambiguous | 0.395 | ambiguous | 0.309 | Stabilizing | 0.717 | D | 0.667 | prob.neutral | None | None | None | None | N |
| S/M | 0.542 | ambiguous | 0.5281 | ambiguous | 0.217 | Stabilizing | 0.998 | D | 0.707 | prob.delet. | None | None | None | None | N |
| S/N | 0.728 | likely_pathogenic | 0.7151 | pathogenic | -0.657 | Destabilizing | 0.792 | D | 0.727 | deleterious | N | 0.47439007 | None | None | N |
| S/P | 0.9141 | likely_pathogenic | 0.9062 | pathogenic | 0.04 | Stabilizing | 0.973 | D | 0.705 | prob.delet. | None | None | None | None | N |
| S/Q | 0.9635 | likely_pathogenic | 0.9649 | pathogenic | -0.516 | Destabilizing | 0.973 | D | 0.716 | prob.delet. | None | None | None | None | N |
| S/R | 0.992 | likely_pathogenic | 0.9921 | pathogenic | -0.546 | Destabilizing | 0.931 | D | 0.709 | prob.delet. | N | 0.496595702 | None | None | N |
| S/T | 0.1772 | likely_benign | 0.1695 | benign | -0.499 | Destabilizing | 0.012 | N | 0.403 | neutral | N | 0.43076103 | None | None | N |
| S/V | 0.578 | likely_pathogenic | 0.5464 | ambiguous | 0.04 | Stabilizing | 0.899 | D | 0.676 | prob.neutral | None | None | None | None | N |
| S/W | 0.9192 | likely_pathogenic | 0.9157 | pathogenic | -0.557 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | N |
| S/Y | 0.8333 | likely_pathogenic | 0.8288 | pathogenic | -0.167 | Destabilizing | 0.991 | D | 0.788 | deleterious | 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.