Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23712 | 71359;71360;71361 | chr2:178574998;178574997;178574996 | chr2:179439725;179439724;179439723 |
| N2AB | 22071 | 66436;66437;66438 | chr2:178574998;178574997;178574996 | chr2:179439725;179439724;179439723 |
| N2A | 21144 | 63655;63656;63657 | chr2:178574998;178574997;178574996 | chr2:179439725;179439724;179439723 |
| N2B | 14647 | 44164;44165;44166 | chr2:178574998;178574997;178574996 | chr2:179439725;179439724;179439723 |
| Novex-1 | 14772 | 44539;44540;44541 | chr2:178574998;178574997;178574996 | chr2:179439725;179439724;179439723 |
| Novex-2 | 14839 | 44740;44741;44742 | chr2:178574998;178574997;178574996 | chr2:179439725;179439724;179439723 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1275870840  |
-0.115 | 0.309 | N | 0.435 | 0.236 | 0.475895305069 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66334E-04 |
| V/A | rs1275870840 |
-0.115 | 0.309 | N | 0.435 | 0.236 | 0.475895305069 | gnomAD-4.0.0 | 3.18443E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.83325E-04 | 0 | 0 | 0 |
| V/I | rs879054551 |
None | 0.007 | N | 0.313 | 0.098 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/I | rs879054551 |
None | 0.007 | N | 0.313 | 0.098 | None | gnomAD-4.0.0 | 8.05831E-06 | None | None | None | None | I | None | 1.3354E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01727E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1541 | likely_benign | 0.1264 | benign | -0.42 | Destabilizing | 0.309 | N | 0.435 | neutral | N | 0.466775837 | None | None | I |
| V/C | 0.7411 | likely_pathogenic | 0.7089 | pathogenic | -0.889 | Destabilizing | 0.996 | D | 0.598 | neutral | None | None | None | None | I |
| V/D | 0.8121 | likely_pathogenic | 0.7374 | pathogenic | -0.262 | Destabilizing | 0.91 | D | 0.585 | neutral | None | None | None | None | I |
| V/E | 0.707 | likely_pathogenic | 0.6141 | pathogenic | -0.368 | Destabilizing | 0.521 | D | 0.57 | neutral | D | 0.523151982 | None | None | I |
| V/F | 0.2576 | likely_benign | 0.1969 | benign | -0.738 | Destabilizing | 0.91 | D | 0.551 | neutral | None | None | None | None | I |
| V/G | 0.3948 | ambiguous | 0.3372 | benign | -0.483 | Destabilizing | 0.884 | D | 0.566 | neutral | D | 0.522458548 | None | None | I |
| V/H | 0.7725 | likely_pathogenic | 0.7031 | pathogenic | -0.044 | Destabilizing | 0.987 | D | 0.608 | neutral | None | None | None | None | I |
| V/I | 0.0995 | likely_benign | 0.0937 | benign | -0.388 | Destabilizing | 0.007 | N | 0.313 | neutral | N | 0.512684272 | None | None | I |
| V/K | 0.7366 | likely_pathogenic | 0.6425 | pathogenic | -0.426 | Destabilizing | 0.009 | N | 0.519 | neutral | None | None | None | None | I |
| V/L | 0.2972 | likely_benign | 0.2266 | benign | -0.388 | Destabilizing | 0.003 | N | 0.271 | neutral | N | 0.432625978 | None | None | I |
| V/M | 0.2305 | likely_benign | 0.187 | benign | -0.643 | Destabilizing | 0.91 | D | 0.481 | neutral | None | None | None | None | I |
| V/N | 0.5835 | likely_pathogenic | 0.5106 | ambiguous | -0.281 | Destabilizing | 0.91 | D | 0.593 | neutral | None | None | None | None | I |
| V/P | 0.8861 | likely_pathogenic | 0.8264 | pathogenic | -0.371 | Destabilizing | 0.953 | D | 0.607 | neutral | None | None | None | None | I |
| V/Q | 0.6163 | likely_pathogenic | 0.5389 | ambiguous | -0.459 | Destabilizing | 0.91 | D | 0.606 | neutral | None | None | None | None | I |
| V/R | 0.6373 | likely_pathogenic | 0.524 | ambiguous | 0.001 | Stabilizing | 0.835 | D | 0.581 | neutral | None | None | None | None | I |
| V/S | 0.2836 | likely_benign | 0.2481 | benign | -0.614 | Destabilizing | 0.742 | D | 0.56 | neutral | None | None | None | None | I |
| V/T | 0.1871 | likely_benign | 0.1661 | benign | -0.625 | Destabilizing | 0.742 | D | 0.405 | neutral | None | None | None | None | I |
| V/W | 0.9052 | likely_pathogenic | 0.862 | pathogenic | -0.788 | Destabilizing | 0.996 | D | 0.631 | neutral | None | None | None | None | I |
| V/Y | 0.7527 | likely_pathogenic | 0.6758 | pathogenic | -0.53 | Destabilizing | 0.984 | D | 0.552 | 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.