Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14774 | 44545;44546;44547 | chr2:178629405;178629404;178629403 | chr2:179494132;179494131;179494130 |
| N2AB | 13133 | 39622;39623;39624 | chr2:178629405;178629404;178629403 | chr2:179494132;179494131;179494130 |
| N2A | 12206 | 36841;36842;36843 | chr2:178629405;178629404;178629403 | chr2:179494132;179494131;179494130 |
| N2B | 5709 | 17350;17351;17352 | chr2:178629405;178629404;178629403 | chr2:179494132;179494131;179494130 |
| Novex-1 | 5834 | 17725;17726;17727 | chr2:178629405;178629404;178629403 | chr2:179494132;179494131;179494130 |
| Novex-2 | 5901 | 17926;17927;17928 | chr2:178629405;178629404;178629403 | chr2:179494132;179494131;179494130 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs748139496  |
-0.01 | 0.999 | N | 0.516 | 0.327 | 0.355034743287 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/A | rs748139496 |
-0.01 | 0.999 | N | 0.516 | 0.327 | 0.355034743287 | gnomAD-4.0.0 | 3.18608E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86664E-05 | 0 |
| T/I | rs930837832 |
0.074 | 1.0 | D | 0.638 | 0.479 | 0.642532236133 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/I | rs930837832 |
0.074 | 1.0 | D | 0.638 | 0.479 | 0.642532236133 | gnomAD-4.0.0 | 1.5931E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86174E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1308 | likely_benign | 0.1189 | benign | -0.187 | Destabilizing | 0.999 | D | 0.516 | neutral | N | 0.501949693 | None | None | N |
| T/C | 0.6696 | likely_pathogenic | 0.5868 | pathogenic | -0.569 | Destabilizing | 1.0 | D | 0.557 | neutral | None | None | None | None | N |
| T/D | 0.5277 | ambiguous | 0.5046 | ambiguous | -0.07 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| T/E | 0.3423 | ambiguous | 0.3148 | benign | -0.151 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/F | 0.4004 | ambiguous | 0.3421 | ambiguous | -0.882 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| T/G | 0.5117 | ambiguous | 0.4858 | ambiguous | -0.24 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| T/H | 0.41 | ambiguous | 0.3567 | ambiguous | -0.35 | Destabilizing | 1.0 | D | 0.574 | neutral | None | None | None | None | N |
| T/I | 0.2535 | likely_benign | 0.2124 | benign | -0.169 | Destabilizing | 1.0 | D | 0.638 | neutral | D | 0.59075454 | None | None | N |
| T/K | 0.3397 | likely_benign | 0.3144 | benign | -0.362 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| T/L | 0.1816 | likely_benign | 0.1585 | benign | -0.169 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| T/M | 0.1215 | likely_benign | 0.1069 | benign | -0.345 | Destabilizing | 1.0 | D | 0.571 | neutral | None | None | None | None | N |
| T/N | 0.1873 | likely_benign | 0.1865 | benign | -0.307 | Destabilizing | 1.0 | D | 0.642 | neutral | N | 0.502501557 | None | None | N |
| T/P | 0.3616 | ambiguous | 0.3612 | ambiguous | -0.152 | Destabilizing | 1.0 | D | 0.621 | neutral | D | 0.670519881 | None | None | N |
| T/Q | 0.3186 | likely_benign | 0.2925 | benign | -0.455 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| T/R | 0.3002 | likely_benign | 0.2538 | benign | -0.078 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| T/S | 0.1678 | likely_benign | 0.1534 | benign | -0.426 | Destabilizing | 0.999 | D | 0.528 | neutral | N | 0.510958451 | None | None | N |
| T/V | 0.1936 | likely_benign | 0.1617 | benign | -0.152 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| T/W | 0.7894 | likely_pathogenic | 0.7046 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| T/Y | 0.46 | ambiguous | 0.406 | ambiguous | -0.665 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | 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.