Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15265 | 46018;46019;46020 | chr2:178620817;178620816;178620815 | chr2:179485544;179485543;179485542 |
| N2AB | 13624 | 41095;41096;41097 | chr2:178620817;178620816;178620815 | chr2:179485544;179485543;179485542 |
| N2A | 12697 | 38314;38315;38316 | chr2:178620817;178620816;178620815 | chr2:179485544;179485543;179485542 |
| N2B | 6200 | 18823;18824;18825 | chr2:178620817;178620816;178620815 | chr2:179485544;179485543;179485542 |
| Novex-1 | 6325 | 19198;19199;19200 | chr2:178620817;178620816;178620815 | chr2:179485544;179485543;179485542 |
| Novex-2 | 6392 | 19399;19400;19401 | chr2:178620817;178620816;178620815 | chr2:179485544;179485543;179485542 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs764279926  |
-1.732 | 0.822 | D | 0.611 | 0.529 | 0.693294191124 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs764279926 |
-1.732 | 0.822 | D | 0.611 | 0.529 | 0.693294191124 | gnomAD-4.0.0 | 3.42291E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63876E-05 | 1.65848E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8206 | likely_pathogenic | 0.8023 | pathogenic | -1.269 | Destabilizing | 0.754 | D | 0.603 | neutral | None | None | None | None | N |
| R/C | 0.3331 | likely_benign | 0.3352 | benign | -1.286 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| R/D | 0.9631 | likely_pathogenic | 0.9597 | pathogenic | -0.201 | Destabilizing | 0.956 | D | 0.653 | neutral | None | None | None | None | N |
| R/E | 0.7253 | likely_pathogenic | 0.7162 | pathogenic | -0.031 | Destabilizing | 0.86 | D | 0.557 | neutral | None | None | None | None | N |
| R/F | 0.8435 | likely_pathogenic | 0.8363 | pathogenic | -0.799 | Destabilizing | 0.978 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/G | 0.7791 | likely_pathogenic | 0.7536 | pathogenic | -1.624 | Destabilizing | 0.822 | D | 0.611 | neutral | D | 0.605246877 | None | None | N |
| R/H | 0.1798 | likely_benign | 0.1928 | benign | -1.633 | Destabilizing | 0.998 | D | 0.6 | neutral | None | None | None | None | N |
| R/I | 0.4701 | ambiguous | 0.4658 | ambiguous | -0.282 | Destabilizing | 0.89 | D | 0.687 | prob.neutral | N | 0.486499235 | None | None | N |
| R/K | 0.1995 | likely_benign | 0.212 | benign | -1.165 | Destabilizing | 0.656 | D | 0.547 | neutral | N | 0.513716677 | None | None | N |
| R/L | 0.5029 | ambiguous | 0.4865 | ambiguous | -0.282 | Destabilizing | 0.754 | D | 0.605 | neutral | None | None | None | None | N |
| R/M | 0.5583 | ambiguous | 0.5554 | ambiguous | -0.701 | Destabilizing | 0.994 | D | 0.671 | neutral | None | None | None | None | N |
| R/N | 0.8967 | likely_pathogenic | 0.8926 | pathogenic | -0.739 | Destabilizing | 0.956 | D | 0.603 | neutral | None | None | None | None | N |
| R/P | 0.9901 | likely_pathogenic | 0.99 | pathogenic | -0.593 | Destabilizing | 0.978 | D | 0.686 | prob.neutral | None | None | None | None | N |
| R/Q | 0.1881 | likely_benign | 0.2024 | benign | -0.807 | Destabilizing | 0.978 | D | 0.621 | neutral | None | None | None | None | N |
| R/S | 0.8506 | likely_pathogenic | 0.8325 | pathogenic | -1.656 | Destabilizing | 0.698 | D | 0.596 | neutral | D | 0.559644948 | None | None | N |
| R/T | 0.5803 | likely_pathogenic | 0.5469 | ambiguous | -1.279 | Destabilizing | 0.014 | N | 0.4 | neutral | N | 0.49906526 | None | None | N |
| R/V | 0.5891 | likely_pathogenic | 0.5819 | pathogenic | -0.593 | Destabilizing | 0.915 | D | 0.651 | neutral | None | None | None | None | N |
| R/W | 0.3667 | ambiguous | 0.3643 | ambiguous | -0.307 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| R/Y | 0.6838 | likely_pathogenic | 0.6881 | pathogenic | -0.088 | Destabilizing | 0.993 | D | 0.691 | prob.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.