Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27890 | 83893;83894;83895 | chr2:178562464;178562463;178562462 | chr2:179427191;179427190;179427189 |
| N2AB | 26249 | 78970;78971;78972 | chr2:178562464;178562463;178562462 | chr2:179427191;179427190;179427189 |
| N2A | 25322 | 76189;76190;76191 | chr2:178562464;178562463;178562462 | chr2:179427191;179427190;179427189 |
| N2B | 18825 | 56698;56699;56700 | chr2:178562464;178562463;178562462 | chr2:179427191;179427190;179427189 |
| Novex-1 | 18950 | 57073;57074;57075 | chr2:178562464;178562463;178562462 | chr2:179427191;179427190;179427189 |
| Novex-2 | 19017 | 57274;57275;57276 | chr2:178562464;178562463;178562462 | chr2:179427191;179427190;179427189 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs757900483  |
-0.909 | 0.242 | N | 0.452 | 0.417 | 0.313518423057 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| D/H | rs757900483 |
-0.909 | 0.242 | N | 0.452 | 0.417 | 0.313518423057 | gnomAD-4.0.0 | 6.84417E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99583E-07 | 0 | 0 |
| D/N | None | None | 0.762 | N | 0.71 | 0.286 | 0.325263233342 | gnomAD-4.0.0 | 6.84417E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8395 | likely_pathogenic | 0.9016 | pathogenic | -0.373 | Destabilizing | 0.98 | D | 0.625 | neutral | N | 0.492070387 | None | None | N |
| D/C | 0.9654 | likely_pathogenic | 0.9812 | pathogenic | 0.127 | Stabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| D/E | 0.8237 | likely_pathogenic | 0.8706 | pathogenic | -0.574 | Destabilizing | 0.617 | D | 0.423 | neutral | N | 0.493854359 | None | None | N |
| D/F | 0.9733 | likely_pathogenic | 0.9855 | pathogenic | -0.524 | Destabilizing | 0.998 | D | 0.652 | neutral | None | None | None | None | N |
| D/G | 0.8207 | likely_pathogenic | 0.8889 | pathogenic | -0.618 | Destabilizing | 0.912 | D | 0.615 | neutral | N | 0.512353916 | None | None | N |
| D/H | 0.9151 | likely_pathogenic | 0.9484 | pathogenic | -0.827 | Destabilizing | 0.242 | N | 0.452 | neutral | N | 0.507808012 | None | None | N |
| D/I | 0.9516 | likely_pathogenic | 0.974 | pathogenic | 0.239 | Stabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| D/K | 0.966 | likely_pathogenic | 0.9824 | pathogenic | 0.157 | Stabilizing | 0.996 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/L | 0.9438 | likely_pathogenic | 0.9654 | pathogenic | 0.239 | Stabilizing | 0.996 | D | 0.643 | neutral | None | None | None | None | N |
| D/M | 0.978 | likely_pathogenic | 0.9876 | pathogenic | 0.679 | Stabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| D/N | 0.2582 | likely_benign | 0.307 | benign | -0.14 | Destabilizing | 0.762 | D | 0.71 | prob.delet. | N | 0.519271023 | None | None | N |
| D/P | 0.9769 | likely_pathogenic | 0.9869 | pathogenic | 0.058 | Stabilizing | 0.967 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/Q | 0.9482 | likely_pathogenic | 0.9693 | pathogenic | -0.091 | Destabilizing | 0.989 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/R | 0.96 | likely_pathogenic | 0.9787 | pathogenic | 0.078 | Stabilizing | 0.996 | D | 0.668 | neutral | None | None | None | None | N |
| D/S | 0.5123 | ambiguous | 0.6141 | pathogenic | -0.278 | Destabilizing | 0.95 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/T | 0.7111 | likely_pathogenic | 0.8098 | pathogenic | -0.077 | Destabilizing | 0.984 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/V | 0.8877 | likely_pathogenic | 0.9359 | pathogenic | 0.058 | Stabilizing | 0.985 | D | 0.645 | neutral | N | 0.507301033 | None | None | N |
| D/W | 0.9951 | likely_pathogenic | 0.9971 | pathogenic | -0.465 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| D/Y | 0.8509 | likely_pathogenic | 0.9105 | pathogenic | -0.299 | Destabilizing | 0.989 | D | 0.652 | neutral | D | 0.535066526 | 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.