Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24610 | 74053;74054;74055 | chr2:178572304;178572303;178572302 | chr2:179437031;179437030;179437029 |
| N2AB | 22969 | 69130;69131;69132 | chr2:178572304;178572303;178572302 | chr2:179437031;179437030;179437029 |
| N2A | 22042 | 66349;66350;66351 | chr2:178572304;178572303;178572302 | chr2:179437031;179437030;179437029 |
| N2B | 15545 | 46858;46859;46860 | chr2:178572304;178572303;178572302 | chr2:179437031;179437030;179437029 |
| Novex-1 | 15670 | 47233;47234;47235 | chr2:178572304;178572303;178572302 | chr2:179437031;179437030;179437029 |
| Novex-2 | 15737 | 47434;47435;47436 | chr2:178572304;178572303;178572302 | chr2:179437031;179437030;179437029 |
| 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/C | None | None | 0.998 | N | 0.69 | 0.362 | 0.36893422563 | gnomAD-4.0.0 | 1.59631E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88352E-05 | 0 | 0 | 0 | 0 |
| S/F | None | None | 0.998 | N | 0.826 | 0.383 | 0.335164054921 | gnomAD-4.0.0 | 1.59631E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.42248E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0567 | likely_benign | 0.0578 | benign | -0.559 | Destabilizing | 0.007 | N | 0.279 | neutral | N | 0.388892978 | None | None | N |
| S/C | 0.093 | likely_benign | 0.0884 | benign | -0.371 | Destabilizing | 0.998 | D | 0.69 | prob.delet. | N | 0.505797506 | None | None | N |
| S/D | 0.7934 | likely_pathogenic | 0.7273 | pathogenic | 0.675 | Stabilizing | 0.948 | D | 0.607 | neutral | None | None | None | None | N |
| S/E | 0.7852 | likely_pathogenic | 0.7397 | pathogenic | 0.619 | Stabilizing | 0.962 | D | 0.591 | neutral | None | None | None | None | N |
| S/F | 0.4207 | ambiguous | 0.3242 | benign | -0.924 | Destabilizing | 0.998 | D | 0.826 | deleterious | N | 0.499042105 | None | None | N |
| S/G | 0.1043 | likely_benign | 0.0896 | benign | -0.724 | Destabilizing | 0.893 | D | 0.541 | neutral | None | None | None | None | N |
| S/H | 0.626 | likely_pathogenic | 0.5622 | ambiguous | -1.121 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/I | 0.2736 | likely_benign | 0.198 | benign | -0.246 | Destabilizing | 0.996 | D | 0.789 | deleterious | None | None | None | None | N |
| S/K | 0.9204 | likely_pathogenic | 0.8756 | pathogenic | -0.311 | Destabilizing | 0.971 | D | 0.597 | neutral | None | None | None | None | N |
| S/L | 0.1877 | likely_benign | 0.1465 | benign | -0.246 | Destabilizing | 0.971 | D | 0.779 | deleterious | None | None | None | None | N |
| S/M | 0.2421 | likely_benign | 0.1986 | benign | -0.094 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/N | 0.2635 | likely_benign | 0.2155 | benign | -0.091 | Destabilizing | 0.958 | D | 0.632 | neutral | None | None | None | None | N |
| S/P | 0.0772 | likely_benign | 0.0787 | benign | -0.32 | Destabilizing | 0.009 | N | 0.389 | neutral | N | 0.355399266 | None | None | N |
| S/Q | 0.6897 | likely_pathogenic | 0.6414 | pathogenic | -0.29 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| S/R | 0.8895 | likely_pathogenic | 0.8341 | pathogenic | -0.201 | Destabilizing | 0.996 | D | 0.691 | prob.delet. | None | None | None | None | N |
| S/T | 0.1381 | likely_benign | 0.111 | benign | -0.277 | Destabilizing | 0.442 | N | 0.569 | neutral | N | 0.486518312 | None | None | N |
| S/V | 0.2268 | likely_benign | 0.1822 | benign | -0.32 | Destabilizing | 0.926 | D | 0.783 | deleterious | None | None | None | None | N |
| S/W | 0.6097 | likely_pathogenic | 0.5006 | ambiguous | -0.85 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| S/Y | 0.3761 | ambiguous | 0.3034 | benign | -0.593 | Destabilizing | 0.998 | D | 0.82 | deleterious | N | 0.519361449 | 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.