Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35009 | 105250;105251;105252 | chr2:178531590;178531589;178531588 | chr2:179396317;179396316;179396315 |
| N2AB | 33368 | 100327;100328;100329 | chr2:178531590;178531589;178531588 | chr2:179396317;179396316;179396315 |
| N2A | 32441 | 97546;97547;97548 | chr2:178531590;178531589;178531588 | chr2:179396317;179396316;179396315 |
| N2B | 25944 | 78055;78056;78057 | chr2:178531590;178531589;178531588 | chr2:179396317;179396316;179396315 |
| Novex-1 | 26069 | 78430;78431;78432 | chr2:178531590;178531589;178531588 | chr2:179396317;179396316;179396315 |
| Novex-2 | 26136 | 78631;78632;78633 | chr2:178531590;178531589;178531588 | chr2:179396317;179396316;179396315 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs1689133557  |
None | 0.001 | N | 0.181 | 0.143 | 0.232513804876 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.30856E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs1689133557 |
None | 0.001 | N | 0.181 | 0.143 | 0.232513804876 | gnomAD-4.0.0 | 1.31403E-05 | None | None | None | None | N | None | 0 | 1.30856E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/I | None | None | 0.497 | N | 0.725 | 0.438 | 0.521653710555 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21507E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1569 | likely_benign | 0.1477 | benign | -0.708 | Destabilizing | 0.072 | N | 0.42 | neutral | None | None | None | None | N |
| S/C | 0.2228 | likely_benign | 0.2119 | benign | -0.494 | Destabilizing | 0.958 | D | 0.626 | neutral | N | 0.512323095 | None | None | N |
| S/D | 0.7367 | likely_pathogenic | 0.8124 | pathogenic | -0.987 | Destabilizing | 0.272 | N | 0.445 | neutral | None | None | None | None | N |
| S/E | 0.7347 | likely_pathogenic | 0.7853 | pathogenic | -0.987 | Destabilizing | 0.431 | N | 0.441 | neutral | None | None | None | None | N |
| S/F | 0.8094 | likely_pathogenic | 0.8058 | pathogenic | -1.013 | Destabilizing | 0.89 | D | 0.735 | prob.delet. | None | None | None | None | N |
| S/G | 0.1387 | likely_benign | 0.1293 | benign | -0.952 | Destabilizing | 0.001 | N | 0.181 | neutral | N | 0.516860728 | None | None | N |
| S/H | 0.5791 | likely_pathogenic | 0.638 | pathogenic | -1.53 | Destabilizing | 0.968 | D | 0.617 | neutral | None | None | None | None | N |
| S/I | 0.5155 | ambiguous | 0.5226 | ambiguous | -0.162 | Destabilizing | 0.497 | N | 0.725 | prob.delet. | N | 0.505068167 | None | None | N |
| S/K | 0.7282 | likely_pathogenic | 0.7914 | pathogenic | -0.808 | Destabilizing | 0.272 | N | 0.43 | neutral | None | None | None | None | N |
| S/L | 0.4044 | ambiguous | 0.4182 | ambiguous | -0.162 | Destabilizing | 0.272 | N | 0.599 | neutral | None | None | None | None | N |
| S/M | 0.4752 | ambiguous | 0.4981 | ambiguous | 0.328 | Stabilizing | 0.968 | D | 0.616 | neutral | None | None | None | None | N |
| S/N | 0.3217 | likely_benign | 0.4095 | ambiguous | -0.898 | Destabilizing | 0.22 | N | 0.467 | neutral | N | 0.492697903 | None | None | N |
| S/P | 0.9256 | likely_pathogenic | 0.9398 | pathogenic | -0.311 | Destabilizing | 0.726 | D | 0.629 | neutral | None | None | None | None | N |
| S/Q | 0.5873 | likely_pathogenic | 0.6606 | pathogenic | -1.103 | Destabilizing | 0.726 | D | 0.472 | neutral | None | None | None | None | N |
| S/R | 0.5327 | ambiguous | 0.6063 | pathogenic | -0.641 | Destabilizing | 0.667 | D | 0.628 | neutral | N | 0.492697903 | None | None | N |
| S/T | 0.1667 | likely_benign | 0.1914 | benign | -0.809 | Destabilizing | 0.004 | N | 0.309 | neutral | N | 0.495061303 | None | None | N |
| S/V | 0.5558 | ambiguous | 0.5722 | pathogenic | -0.311 | Destabilizing | 0.567 | D | 0.643 | neutral | None | None | None | None | N |
| S/W | 0.8364 | likely_pathogenic | 0.8385 | pathogenic | -1.045 | Destabilizing | 0.968 | D | 0.753 | deleterious | None | None | None | None | N |
| S/Y | 0.693 | likely_pathogenic | 0.7016 | pathogenic | -0.75 | Destabilizing | 0.89 | D | 0.734 | prob.delet. | 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.