Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17003 | 51232;51233;51234 | chr2:178611122;178611121;178611120 | chr2:179475849;179475848;179475847 |
| N2AB | 15362 | 46309;46310;46311 | chr2:178611122;178611121;178611120 | chr2:179475849;179475848;179475847 |
| N2A | 14435 | 43528;43529;43530 | chr2:178611122;178611121;178611120 | chr2:179475849;179475848;179475847 |
| N2B | 7938 | 24037;24038;24039 | chr2:178611122;178611121;178611120 | chr2:179475849;179475848;179475847 |
| Novex-1 | 8063 | 24412;24413;24414 | chr2:178611122;178611121;178611120 | chr2:179475849;179475848;179475847 |
| Novex-2 | 8130 | 24613;24614;24615 | chr2:178611122;178611121;178611120 | chr2:179475849;179475848;179475847 |
| 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 | None | None | 0.425 | N | 0.359 | 0.143 | 0.389750110748 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/R | rs960842817  |
-0.62 | 0.642 | N | 0.481 | 0.398 | 0.633704164295 | 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 |
| M/R | rs960842817 |
-0.62 | 0.642 | N | 0.481 | 0.398 | 0.633704164295 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/R | rs960842817 |
-0.62 | 0.642 | N | 0.481 | 0.398 | 0.633704164295 | gnomAD-4.0.0 | 1.67419E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.2896E-05 | 0 | 0 |
| M/V | rs988593796 |
-1.647 | 0.425 | N | 0.316 | 0.207 | 0.376393476264 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| M/V | rs988593796 |
-1.647 | 0.425 | N | 0.316 | 0.207 | 0.376393476264 | gnomAD-4.0.0 | 3.42289E-06 | None | None | None | None | N | None | 2.99258E-05 | 0 | None | 0 | 2.52845E-05 | None | 0 | 0 | 8.99844E-07 | 2.31943E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4131 | ambiguous | 0.4834 | ambiguous | -2.295 | Highly Destabilizing | 0.495 | N | 0.3 | neutral | None | None | None | None | N |
| M/C | 0.6444 | likely_pathogenic | 0.6658 | pathogenic | -1.536 | Destabilizing | 0.981 | D | 0.495 | neutral | None | None | None | None | N |
| M/D | 0.9111 | likely_pathogenic | 0.9392 | pathogenic | -1.052 | Destabilizing | 0.003 | N | 0.371 | neutral | None | None | None | None | N |
| M/E | 0.5571 | ambiguous | 0.6263 | pathogenic | -0.958 | Destabilizing | 0.013 | N | 0.295 | neutral | None | None | None | None | N |
| M/F | 0.2903 | likely_benign | 0.3219 | benign | -1.009 | Destabilizing | 0.003 | N | 0.139 | neutral | None | None | None | None | N |
| M/G | 0.6573 | likely_pathogenic | 0.721 | pathogenic | -2.679 | Highly Destabilizing | 0.665 | D | 0.409 | neutral | None | None | None | None | N |
| M/H | 0.5886 | likely_pathogenic | 0.6478 | pathogenic | -1.757 | Destabilizing | 0.007 | N | 0.387 | neutral | None | None | None | None | N |
| M/I | 0.2635 | likely_benign | 0.3065 | benign | -1.249 | Destabilizing | 0.425 | N | 0.359 | neutral | N | 0.428693803 | None | None | N |
| M/K | 0.2695 | likely_benign | 0.3283 | benign | -1.065 | Destabilizing | 0.425 | N | 0.399 | neutral | N | 0.512922813 | None | None | N |
| M/L | 0.1293 | likely_benign | 0.1395 | benign | -1.249 | Destabilizing | 0.139 | N | 0.244 | neutral | N | 0.438640558 | None | None | N |
| M/N | 0.6972 | likely_pathogenic | 0.7742 | pathogenic | -1.018 | Destabilizing | 0.704 | D | 0.492 | neutral | None | None | None | None | N |
| M/P | 0.9182 | likely_pathogenic | 0.9422 | pathogenic | -1.574 | Destabilizing | 0.936 | D | 0.584 | neutral | None | None | None | None | N |
| M/Q | 0.305 | likely_benign | 0.3417 | ambiguous | -0.99 | Destabilizing | 0.704 | D | 0.368 | neutral | None | None | None | None | N |
| M/R | 0.2726 | likely_benign | 0.3143 | benign | -0.671 | Destabilizing | 0.642 | D | 0.481 | neutral | N | 0.514279603 | None | None | N |
| M/S | 0.511 | ambiguous | 0.5838 | pathogenic | -1.667 | Destabilizing | 0.495 | N | 0.351 | neutral | None | None | None | None | N |
| M/T | 0.2702 | likely_benign | 0.3097 | benign | -1.453 | Destabilizing | 0.6 | D | 0.423 | neutral | N | 0.450857192 | None | None | N |
| M/V | 0.082 | likely_benign | 0.083 | benign | -1.574 | Destabilizing | 0.425 | N | 0.316 | neutral | N | 0.441995015 | None | None | N |
| M/W | 0.6005 | likely_pathogenic | 0.6323 | pathogenic | -0.986 | Destabilizing | 0.995 | D | 0.489 | neutral | None | None | None | None | N |
| M/Y | 0.577 | likely_pathogenic | 0.6221 | pathogenic | -1.078 | Destabilizing | 0.543 | D | 0.469 | 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.