Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7128 | 21607;21608;21609 | chr2:178723877;178723876;178723875 | chr2:179588604;179588603;179588602 |
| N2AB | 6811 | 20656;20657;20658 | chr2:178723877;178723876;178723875 | chr2:179588604;179588603;179588602 |
| N2A | 5884 | 17875;17876;17877 | chr2:178723877;178723876;178723875 | chr2:179588604;179588603;179588602 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs727505031  |
-0.11 | 0.998 | N | 0.588 | 0.284 | 0.702784494799 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.87E-05 | None | 0 | 8.94E-06 | 0 |
| R/C | rs727505031 |
-0.11 | 0.998 | N | 0.588 | 0.284 | 0.702784494799 | gnomAD-4.0.0 | 4.79626E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70187E-06 | 3.48578E-05 | 1.6592E-05 |
| R/G | rs727505031 |
None | 0.39 | N | 0.525 | 0.279 | 0.553996833274 | gnomAD-4.0.0 | 6.85179E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16193E-05 | 0 |
| R/H | rs768531006 |
-1.074 | 0.98 | N | 0.611 | 0.245 | None | gnomAD-2.1.1 | 2.87E-05 | None | None | None | None | I | None | 8.27E-05 | 5.67E-05 | None | 0 | 0 | None | 6.6E-05 | None | 0 | 1.57E-05 | 0 |
| R/H | rs768531006 |
-1.074 | 0.98 | N | 0.611 | 0.245 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs768531006 |
-1.074 | 0.98 | N | 0.611 | 0.245 | None | gnomAD-4.0.0 | 1.11711E-05 | None | None | None | None | I | None | 2.6718E-05 | 3.3389E-05 | None | 0 | 2.23065E-05 | None | 0 | 0 | 8.48791E-06 | 2.20216E-05 | 1.60385E-05 |
| R/L | None | None | 0.756 | N | 0.573 | 0.294 | 0.557325494615 | gnomAD-4.0.0 | 6.8534E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00799E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1309 | likely_benign | 0.1296 | benign | -0.383 | Destabilizing | 0.25 | N | 0.433 | neutral | None | None | None | None | I |
| R/C | 0.1443 | likely_benign | 0.1496 | benign | -0.262 | Destabilizing | 0.998 | D | 0.588 | neutral | N | 0.497869535 | None | None | I |
| R/D | 0.2705 | likely_benign | 0.2473 | benign | -0.083 | Destabilizing | 0.617 | D | 0.58 | neutral | None | None | None | None | I |
| R/E | 0.1444 | likely_benign | 0.1433 | benign | 0.006 | Stabilizing | 0.25 | N | 0.529 | neutral | None | None | None | None | I |
| R/F | 0.2907 | likely_benign | 0.2833 | benign | -0.398 | Destabilizing | 0.92 | D | 0.601 | neutral | None | None | None | None | I |
| R/G | 0.0898 | likely_benign | 0.0869 | benign | -0.652 | Destabilizing | 0.39 | N | 0.525 | neutral | N | 0.508046456 | None | None | I |
| R/H | 0.0727 | likely_benign | 0.0736 | benign | -1.102 | Destabilizing | 0.98 | D | 0.611 | neutral | N | 0.481014571 | None | None | I |
| R/I | 0.1491 | likely_benign | 0.1512 | benign | 0.318 | Stabilizing | 0.92 | D | 0.616 | neutral | None | None | None | None | I |
| R/K | 0.0817 | likely_benign | 0.0839 | benign | -0.451 | Destabilizing | 0.002 | N | 0.25 | neutral | None | None | None | None | I |
| R/L | 0.1298 | likely_benign | 0.1286 | benign | 0.318 | Stabilizing | 0.756 | D | 0.573 | neutral | N | 0.486575106 | None | None | I |
| R/M | 0.1329 | likely_benign | 0.1351 | benign | 0.037 | Stabilizing | 0.972 | D | 0.608 | neutral | None | None | None | None | I |
| R/N | 0.2209 | likely_benign | 0.1956 | benign | 0.08 | Stabilizing | 0.447 | N | 0.533 | neutral | None | None | None | None | I |
| R/P | 0.4008 | ambiguous | 0.3841 | ambiguous | 0.106 | Stabilizing | 0.957 | D | 0.627 | neutral | N | 0.516377938 | None | None | I |
| R/Q | 0.0731 | likely_benign | 0.074 | benign | -0.109 | Destabilizing | 0.617 | D | 0.591 | neutral | None | None | None | None | I |
| R/S | 0.1203 | likely_benign | 0.1122 | benign | -0.492 | Destabilizing | 0.006 | N | 0.311 | neutral | N | 0.321551344 | None | None | I |
| R/T | 0.0722 | likely_benign | 0.0736 | benign | -0.245 | Destabilizing | 0.25 | N | 0.499 | neutral | None | None | None | None | I |
| R/V | 0.1783 | likely_benign | 0.1795 | benign | 0.106 | Stabilizing | 0.617 | D | 0.61 | neutral | None | None | None | None | I |
| R/W | 0.1251 | likely_benign | 0.1288 | benign | -0.215 | Destabilizing | 0.992 | D | 0.624 | neutral | None | None | None | None | I |
| R/Y | 0.2294 | likely_benign | 0.2185 | benign | 0.127 | Stabilizing | 0.972 | D | 0.605 | neutral | None | None | None | None | I |
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.