Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25730 | 77413;77414;77415 | chr2:178568944;178568943;178568942 | chr2:179433671;179433670;179433669 |
| N2AB | 24089 | 72490;72491;72492 | chr2:178568944;178568943;178568942 | chr2:179433671;179433670;179433669 |
| N2A | 23162 | 69709;69710;69711 | chr2:178568944;178568943;178568942 | chr2:179433671;179433670;179433669 |
| N2B | 16665 | 50218;50219;50220 | chr2:178568944;178568943;178568942 | chr2:179433671;179433670;179433669 |
| Novex-1 | 16790 | 50593;50594;50595 | chr2:178568944;178568943;178568942 | chr2:179433671;179433670;179433669 |
| Novex-2 | 16857 | 50794;50795;50796 | chr2:178568944;178568943;178568942 | chr2:179433671;179433670;179433669 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.999 | N | 0.739 | 0.518 | 0.720195407567 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79919E-06 | 0 | 0 |
| I/V | rs745981754  |
-1.542 | 0.088 | N | 0.239 | 0.112 | 0.491660673884 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 1.44852E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs745981754 |
-1.542 | 0.088 | N | 0.239 | 0.112 | 0.491660673884 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 1.31216E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs745981754 |
-1.542 | 0.088 | N | 0.239 | 0.112 | 0.491660673884 | gnomAD-4.0.0 | 9.29762E-06 | None | None | None | None | N | None | 0 | 1.8345E-04 | None | 0 | 0 | None | 0 | 1.64582E-04 | 2.54326E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9833 | likely_pathogenic | 0.9792 | pathogenic | -2.459 | Highly Destabilizing | 0.998 | D | 0.642 | neutral | None | None | None | None | N |
| I/C | 0.9879 | likely_pathogenic | 0.9833 | pathogenic | -1.473 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| I/D | 0.9982 | likely_pathogenic | 0.9966 | pathogenic | -2.455 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/E | 0.9958 | likely_pathogenic | 0.9941 | pathogenic | -2.317 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| I/F | 0.9502 | likely_pathogenic | 0.9337 | pathogenic | -1.576 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | N | 0.516143032 | None | None | N |
| I/G | 0.9961 | likely_pathogenic | 0.9949 | pathogenic | -2.928 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| I/H | 0.9975 | likely_pathogenic | 0.9951 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| I/K | 0.994 | likely_pathogenic | 0.9919 | pathogenic | -1.869 | Destabilizing | 0.997 | D | 0.796 | deleterious | None | None | None | None | N |
| I/L | 0.4879 | ambiguous | 0.4879 | ambiguous | -1.145 | Destabilizing | 0.54 | D | 0.423 | neutral | D | 0.523930268 | None | None | N |
| I/M | 0.62 | likely_pathogenic | 0.589 | pathogenic | -0.825 | Destabilizing | 0.997 | D | 0.696 | prob.neutral | D | 0.534807172 | None | None | N |
| I/N | 0.954 | likely_pathogenic | 0.8676 | pathogenic | -1.933 | Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.524464825 | None | None | N |
| I/P | 0.9809 | likely_pathogenic | 0.9715 | pathogenic | -1.56 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| I/Q | 0.9955 | likely_pathogenic | 0.9927 | pathogenic | -1.955 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| I/R | 0.9932 | likely_pathogenic | 0.9895 | pathogenic | -1.352 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| I/S | 0.9856 | likely_pathogenic | 0.9759 | pathogenic | -2.603 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.526666871 | None | None | N |
| I/T | 0.969 | likely_pathogenic | 0.9593 | pathogenic | -2.338 | Highly Destabilizing | 0.993 | D | 0.749 | deleterious | D | 0.535060662 | None | None | N |
| I/V | 0.1314 | likely_benign | 0.1606 | benign | -1.56 | Destabilizing | 0.088 | N | 0.239 | neutral | N | 0.509595534 | None | None | N |
| I/W | 0.9987 | likely_pathogenic | 0.9975 | pathogenic | -1.875 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9917 | likely_pathogenic | 0.985 | pathogenic | -1.627 | Destabilizing | 0.998 | D | 0.743 | 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.