Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29583 | 88972;88973;88974 | chr2:178554600;178554599;178554598 | chr2:179419327;179419326;179419325 |
| N2AB | 27942 | 84049;84050;84051 | chr2:178554600;178554599;178554598 | chr2:179419327;179419326;179419325 |
| N2A | 27015 | 81268;81269;81270 | chr2:178554600;178554599;178554598 | chr2:179419327;179419326;179419325 |
| N2B | 20518 | 61777;61778;61779 | chr2:178554600;178554599;178554598 | chr2:179419327;179419326;179419325 |
| Novex-1 | 20643 | 62152;62153;62154 | chr2:178554600;178554599;178554598 | chr2:179419327;179419326;179419325 |
| Novex-2 | 20710 | 62353;62354;62355 | chr2:178554600;178554599;178554598 | chr2:179419327;179419326;179419325 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1224789093  |
-0.095 | None | N | 0.105 | 0.145 | 0.526181570707 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| M/I | rs1224789093 |
-0.095 | None | N | 0.105 | 0.145 | 0.526181570707 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85778E-06 | 0 | 0 |
| M/T | None | None | 0.049 | N | 0.386 | 0.245 | 0.551220473365 | gnomAD-4.0.0 | 1.591E-06 | None | None | None | None | I | None | 0 | 2.28634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs377535587 |
-0.439 | None | N | 0.107 | 0.133 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 2.58298E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| M/V | rs377535587 |
-0.439 | None | N | 0.107 | 0.133 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 1.2068E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs377535587 |
-0.439 | None | N | 0.107 | 0.133 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| M/V | rs377535587 |
-0.439 | None | N | 0.107 | 0.133 | None | gnomAD-4.0.0 | 6.81562E-06 | None | None | None | None | I | None | 6.664E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54267E-06 | 0 | 4.80123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.216 | likely_benign | 0.2341 | benign | -1.132 | Destabilizing | 0.006 | N | 0.277 | neutral | None | None | None | None | I |
| M/C | 0.6211 | likely_pathogenic | 0.6304 | pathogenic | -0.858 | Destabilizing | 0.54 | D | 0.449 | neutral | None | None | None | None | I |
| M/D | 0.7563 | likely_pathogenic | 0.7569 | pathogenic | -0.057 | Destabilizing | 0.251 | N | 0.586 | neutral | None | None | None | None | I |
| M/E | 0.4092 | ambiguous | 0.4245 | ambiguous | -0.072 | Destabilizing | 0.251 | N | 0.53 | neutral | None | None | None | None | I |
| M/F | 0.3904 | ambiguous | 0.4058 | ambiguous | -0.422 | Destabilizing | 0.064 | N | 0.298 | neutral | None | None | None | None | I |
| M/G | 0.4832 | ambiguous | 0.5127 | ambiguous | -1.387 | Destabilizing | 0.121 | N | 0.501 | neutral | None | None | None | None | I |
| M/H | 0.4542 | ambiguous | 0.4568 | ambiguous | -0.456 | Destabilizing | 0.781 | D | 0.522 | neutral | None | None | None | None | I |
| M/I | 0.1687 | likely_benign | 0.1907 | benign | -0.518 | Destabilizing | None | N | 0.105 | neutral | N | 0.376046684 | None | None | I |
| M/K | 0.1598 | likely_benign | 0.1647 | benign | -0.034 | Destabilizing | 0.094 | N | 0.459 | neutral | N | 0.389013195 | None | None | I |
| M/L | 0.0873 | likely_benign | 0.0883 | benign | -0.518 | Destabilizing | None | N | 0.095 | neutral | N | 0.398942187 | None | None | I |
| M/N | 0.3725 | ambiguous | 0.381 | ambiguous | 0.132 | Stabilizing | 0.505 | D | 0.606 | neutral | None | None | None | None | I |
| M/P | 0.4613 | ambiguous | 0.4852 | ambiguous | -0.694 | Destabilizing | 0.505 | D | 0.572 | neutral | None | None | None | None | I |
| M/Q | 0.2223 | likely_benign | 0.2305 | benign | -0.015 | Destabilizing | 0.505 | D | 0.375 | neutral | None | None | None | None | I |
| M/R | 0.1908 | likely_benign | 0.1983 | benign | 0.472 | Stabilizing | 0.202 | N | 0.479 | neutral | N | 0.403481215 | None | None | I |
| M/S | 0.3001 | likely_benign | 0.3211 | benign | -0.434 | Destabilizing | 0.064 | N | 0.431 | neutral | None | None | None | None | I |
| M/T | 0.1151 | likely_benign | 0.1218 | benign | -0.342 | Destabilizing | 0.049 | N | 0.386 | neutral | N | 0.356727418 | None | None | I |
| M/V | 0.0534 | likely_benign | 0.0564 | benign | -0.694 | Destabilizing | None | N | 0.107 | neutral | N | 0.365405616 | None | None | I |
| M/W | 0.6818 | likely_pathogenic | 0.7034 | pathogenic | -0.345 | Destabilizing | 0.931 | D | 0.448 | neutral | None | None | None | None | I |
| M/Y | 0.6221 | likely_pathogenic | 0.6308 | pathogenic | -0.293 | Destabilizing | 0.251 | N | 0.489 | 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.