Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23770 | 71533;71534;71535 | chr2:178574824;178574823;178574822 | chr2:179439551;179439550;179439549 |
| N2AB | 22129 | 66610;66611;66612 | chr2:178574824;178574823;178574822 | chr2:179439551;179439550;179439549 |
| N2A | 21202 | 63829;63830;63831 | chr2:178574824;178574823;178574822 | chr2:179439551;179439550;179439549 |
| N2B | 14705 | 44338;44339;44340 | chr2:178574824;178574823;178574822 | chr2:179439551;179439550;179439549 |
| Novex-1 | 14830 | 44713;44714;44715 | chr2:178574824;178574823;178574822 | chr2:179439551;179439550;179439549 |
| Novex-2 | 14897 | 44914;44915;44916 | chr2:178574824;178574823;178574822 | chr2:179439551;179439550;179439549 |
| 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/E | rs1320217778  |
0.107 | 0.625 | N | 0.356 | 0.102 | 0.250579442822 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| D/E | rs1320217778 |
0.107 | 0.625 | N | 0.356 | 0.102 | 0.250579442822 | gnomAD-4.0.0 | 3.18681E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72289E-06 | 0 | 0 |
| D/N | rs747260758 |
0.539 | 0.012 | N | 0.246 | 0.093 | 0.180583059064 | gnomAD-2.1.1 | 5.68E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 4.26425E-04 | None | 0 | 0 | 0 |
| D/N | rs747260758 |
0.539 | 0.012 | N | 0.246 | 0.093 | 0.180583059064 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14079E-04 | 0 |
| D/N | rs747260758 |
0.539 | 0.012 | N | 0.246 | 0.093 | 0.180583059064 | gnomAD-4.0.0 | 3.34813E-05 | None | None | None | None | N | None | 0 | 6.67067E-05 | None | 0 | 0 | None | 0 | 0 | 2.54383E-06 | 4.94516E-04 | 3.20349E-05 |
| D/Y | None | None | 0.989 | D | 0.366 | 0.257 | 0.5711029235 | gnomAD-4.0.0 | 6.8463E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16047E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2037 | likely_benign | 0.1934 | benign | -0.049 | Destabilizing | 0.625 | D | 0.334 | neutral | N | 0.464303174 | None | None | N |
| D/C | 0.7128 | likely_pathogenic | 0.7097 | pathogenic | 0.106 | Stabilizing | 0.998 | D | 0.375 | neutral | None | None | None | None | N |
| D/E | 0.2104 | likely_benign | 0.2038 | benign | -0.278 | Destabilizing | 0.625 | D | 0.356 | neutral | N | 0.470727714 | None | None | N |
| D/F | 0.7514 | likely_pathogenic | 0.7336 | pathogenic | -0.191 | Destabilizing | 0.991 | D | 0.367 | neutral | None | None | None | None | N |
| D/G | 0.1771 | likely_benign | 0.1741 | benign | -0.16 | Destabilizing | 0.669 | D | 0.321 | neutral | N | 0.39699796 | None | None | N |
| D/H | 0.3878 | ambiguous | 0.3838 | ambiguous | 0.23 | Stabilizing | 0.966 | D | 0.298 | neutral | N | 0.458185278 | None | None | N |
| D/I | 0.5017 | ambiguous | 0.481 | ambiguous | 0.174 | Stabilizing | 0.949 | D | 0.379 | neutral | None | None | None | None | N |
| D/K | 0.5245 | ambiguous | 0.521 | ambiguous | 0.549 | Stabilizing | 0.067 | N | 0.24 | neutral | None | None | None | None | N |
| D/L | 0.5045 | ambiguous | 0.4931 | ambiguous | 0.174 | Stabilizing | 0.842 | D | 0.367 | neutral | None | None | None | None | N |
| D/M | 0.6682 | likely_pathogenic | 0.6575 | pathogenic | 0.174 | Stabilizing | 0.998 | D | 0.362 | neutral | None | None | None | None | N |
| D/N | 0.0924 | likely_benign | 0.0898 | benign | 0.34 | Stabilizing | 0.012 | N | 0.246 | neutral | N | 0.458315777 | None | None | N |
| D/P | 0.8337 | likely_pathogenic | 0.819 | pathogenic | 0.119 | Stabilizing | 0.991 | D | 0.297 | neutral | None | None | None | None | N |
| D/Q | 0.4381 | ambiguous | 0.4368 | ambiguous | 0.331 | Stabilizing | 0.949 | D | 0.261 | neutral | None | None | None | None | N |
| D/R | 0.5785 | likely_pathogenic | 0.561 | ambiguous | 0.655 | Stabilizing | 0.728 | D | 0.372 | neutral | None | None | None | None | N |
| D/S | 0.1218 | likely_benign | 0.1161 | benign | 0.259 | Stabilizing | 0.525 | D | 0.333 | neutral | None | None | None | None | N |
| D/T | 0.2043 | likely_benign | 0.1992 | benign | 0.349 | Stabilizing | 0.029 | N | 0.208 | neutral | None | None | None | None | N |
| D/V | 0.3314 | likely_benign | 0.3108 | benign | 0.119 | Stabilizing | 0.801 | D | 0.363 | neutral | N | 0.476154964 | None | None | N |
| D/W | 0.9448 | likely_pathogenic | 0.9462 | pathogenic | -0.151 | Destabilizing | 0.998 | D | 0.486 | neutral | None | None | None | None | N |
| D/Y | 0.3692 | ambiguous | 0.3755 | ambiguous | 0.032 | Stabilizing | 0.989 | D | 0.366 | neutral | D | 0.525159632 | 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.