Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26193 | 78802;78803;78804 | chr2:178567555;178567554;178567553 | chr2:179432282;179432281;179432280 |
| N2AB | 24552 | 73879;73880;73881 | chr2:178567555;178567554;178567553 | chr2:179432282;179432281;179432280 |
| N2A | 23625 | 71098;71099;71100 | chr2:178567555;178567554;178567553 | chr2:179432282;179432281;179432280 |
| N2B | 17128 | 51607;51608;51609 | chr2:178567555;178567554;178567553 | chr2:179432282;179432281;179432280 |
| Novex-1 | 17253 | 51982;51983;51984 | chr2:178567555;178567554;178567553 | chr2:179432282;179432281;179432280 |
| Novex-2 | 17320 | 52183;52184;52185 | chr2:178567555;178567554;178567553 | chr2:179432282;179432281;179432280 |
| 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/L | rs727505241  |
-0.165 | 0.003 | N | 0.12 | 0.168 | 0.405150804464 | gnomAD-2.1.1 | 8.16E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| I/L | rs727505241 |
-0.165 | 0.003 | N | 0.12 | 0.168 | 0.405150804464 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/L | rs727505241 |
-0.165 | 0.003 | N | 0.12 | 0.168 | 0.405150804464 | gnomAD-4.0.0 | 9.94007E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3586E-05 | 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 | 0.9268 | likely_pathogenic | 0.912 | pathogenic | -1.725 | Destabilizing | 0.543 | D | 0.443 | neutral | None | None | None | None | I |
| I/C | 0.9274 | likely_pathogenic | 0.9112 | pathogenic | -1.116 | Destabilizing | 0.02 | N | 0.375 | neutral | None | None | None | None | I |
| I/D | 0.9981 | likely_pathogenic | 0.9978 | pathogenic | -0.978 | Destabilizing | 0.984 | D | 0.448 | neutral | None | None | None | None | I |
| I/E | 0.9959 | likely_pathogenic | 0.9956 | pathogenic | -0.891 | Destabilizing | 0.953 | D | 0.449 | neutral | None | None | None | None | I |
| I/F | 0.5036 | ambiguous | 0.4579 | ambiguous | -1.009 | Destabilizing | 0.521 | D | 0.401 | neutral | D | 0.527093577 | None | None | I |
| I/G | 0.9865 | likely_pathogenic | 0.983 | pathogenic | -2.137 | Highly Destabilizing | 0.854 | D | 0.426 | neutral | None | None | None | None | I |
| I/H | 0.9922 | likely_pathogenic | 0.9903 | pathogenic | -1.397 | Destabilizing | 0.91 | D | 0.425 | neutral | None | None | None | None | I |
| I/K | 0.9922 | likely_pathogenic | 0.9912 | pathogenic | -1.159 | Destabilizing | 0.953 | D | 0.439 | neutral | None | None | None | None | I |
| I/L | 0.2199 | likely_benign | 0.2025 | benign | -0.629 | Destabilizing | 0.003 | N | 0.12 | neutral | N | 0.485132898 | None | None | I |
| I/M | 0.3221 | likely_benign | 0.2933 | benign | -0.598 | Destabilizing | 0.884 | D | 0.45 | neutral | N | 0.514926307 | None | None | I |
| I/N | 0.9741 | likely_pathogenic | 0.9703 | pathogenic | -1.098 | Destabilizing | 0.979 | D | 0.441 | neutral | N | 0.515433286 | None | None | I |
| I/P | 0.9883 | likely_pathogenic | 0.9861 | pathogenic | -0.965 | Destabilizing | 0.984 | D | 0.437 | neutral | None | None | None | None | I |
| I/Q | 0.9916 | likely_pathogenic | 0.9908 | pathogenic | -1.117 | Destabilizing | 0.984 | D | 0.427 | neutral | None | None | None | None | I |
| I/R | 0.9875 | likely_pathogenic | 0.9862 | pathogenic | -0.785 | Destabilizing | 0.953 | D | 0.44 | neutral | None | None | None | None | I |
| I/S | 0.9686 | likely_pathogenic | 0.964 | pathogenic | -1.808 | Destabilizing | 0.815 | D | 0.431 | neutral | N | 0.514672818 | None | None | I |
| I/T | 0.9592 | likely_pathogenic | 0.9546 | pathogenic | -1.581 | Destabilizing | 0.684 | D | 0.43 | neutral | N | 0.514419328 | None | None | I |
| I/V | 0.1516 | likely_benign | 0.1466 | benign | -0.965 | Destabilizing | 0.164 | N | 0.338 | neutral | D | 0.532075322 | None | None | I |
| I/W | 0.9848 | likely_pathogenic | 0.9807 | pathogenic | -1.155 | Destabilizing | 0.987 | D | 0.431 | neutral | None | None | None | None | I |
| I/Y | 0.9354 | likely_pathogenic | 0.9186 | pathogenic | -0.895 | Destabilizing | 0.016 | N | 0.198 | 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.