Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19644 | 59155;59156;59157 | chr2:178593278;178593277;178593276 | chr2:179458005;179458004;179458003 |
| N2AB | 18003 | 54232;54233;54234 | chr2:178593278;178593277;178593276 | chr2:179458005;179458004;179458003 |
| N2A | 17076 | 51451;51452;51453 | chr2:178593278;178593277;178593276 | chr2:179458005;179458004;179458003 |
| N2B | 10579 | 31960;31961;31962 | chr2:178593278;178593277;178593276 | chr2:179458005;179458004;179458003 |
| Novex-1 | 10704 | 32335;32336;32337 | chr2:178593278;178593277;178593276 | chr2:179458005;179458004;179458003 |
| Novex-2 | 10771 | 32536;32537;32538 | chr2:178593278;178593277;178593276 | chr2:179458005;179458004;179458003 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs1173341921  |
None | 0.999 | D | 0.833 | 0.589 | 0.828908509101 | gnomAD-4.0.0 | 3.18397E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77824E-05 | None | 0 | 0 | 0 | 0 | 3.02499E-05 |
| L/P | rs750702045 |
-1.999 | 1.0 | D | 0.851 | 0.833 | 0.938822314792 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| L/P | rs750702045 |
-1.999 | 1.0 | D | 0.851 | 0.833 | 0.938822314792 | gnomAD-4.0.0 | 2.05305E-06 | None | None | None | None | N | None | 0 | 2.23724E-05 | None | 0 | 0 | None | 0 | 0 | 1.79921E-06 | 0 | 0 |
| L/R | rs750702045 |
None | 1.0 | D | 0.847 | 0.847 | 0.919766821495 | gnomAD-4.0.0 | 6.84349E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99604E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9792 | likely_pathogenic | 0.9809 | pathogenic | -2.651 | Highly Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| L/C | 0.9579 | likely_pathogenic | 0.9668 | pathogenic | -2.4 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -3.233 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| L/E | 0.9971 | likely_pathogenic | 0.9966 | pathogenic | -3.07 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/F | 0.8272 | likely_pathogenic | 0.8138 | pathogenic | -1.772 | Destabilizing | 1.0 | D | 0.866 | deleterious | D | 0.66242243 | None | None | N |
| L/G | 0.995 | likely_pathogenic | 0.9948 | pathogenic | -3.149 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/H | 0.9933 | likely_pathogenic | 0.9912 | pathogenic | -2.534 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.679481173 | None | None | N |
| L/I | 0.3011 | likely_benign | 0.3136 | benign | -1.233 | Destabilizing | 0.999 | D | 0.833 | deleterious | D | 0.640286426 | None | None | N |
| L/K | 0.9938 | likely_pathogenic | 0.992 | pathogenic | -2.136 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/M | 0.4672 | ambiguous | 0.4816 | ambiguous | -1.278 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/N | 0.9943 | likely_pathogenic | 0.9941 | pathogenic | -2.421 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/P | 0.997 | likely_pathogenic | 0.9967 | pathogenic | -1.685 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.679481173 | None | None | N |
| L/Q | 0.9897 | likely_pathogenic | 0.9874 | pathogenic | -2.404 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/R | 0.9878 | likely_pathogenic | 0.9842 | pathogenic | -1.674 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.647210287 | None | None | N |
| L/S | 0.9958 | likely_pathogenic | 0.9956 | pathogenic | -3.092 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/T | 0.971 | likely_pathogenic | 0.9736 | pathogenic | -2.788 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| L/V | 0.4368 | ambiguous | 0.4576 | ambiguous | -1.685 | Destabilizing | 0.999 | D | 0.838 | deleterious | D | 0.603715134 | None | None | N |
| L/W | 0.9885 | likely_pathogenic | 0.9853 | pathogenic | -2.117 | Highly Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| L/Y | 0.9851 | likely_pathogenic | 0.9823 | pathogenic | -1.874 | Destabilizing | 1.0 | D | 0.827 | 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.