Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29222 | 87889;87890;87891 | chr2:178557690;178557689;178557688 | chr2:179422417;179422416;179422415 |
| N2AB | 27581 | 82966;82967;82968 | chr2:178557690;178557689;178557688 | chr2:179422417;179422416;179422415 |
| N2A | 26654 | 80185;80186;80187 | chr2:178557690;178557689;178557688 | chr2:179422417;179422416;179422415 |
| N2B | 20157 | 60694;60695;60696 | chr2:178557690;178557689;178557688 | chr2:179422417;179422416;179422415 |
| Novex-1 | 20282 | 61069;61070;61071 | chr2:178557690;178557689;178557688 | chr2:179422417;179422416;179422415 |
| Novex-2 | 20349 | 61270;61271;61272 | chr2:178557690;178557689;178557688 | chr2:179422417;179422416;179422415 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs1421442862  |
-0.808 | 1.0 | N | 0.641 | 0.297 | 0.245101548738 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| D/H | rs1421442862 |
-0.808 | 1.0 | N | 0.641 | 0.297 | 0.245101548738 | gnomAD-4.0.0 | 1.59104E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88232E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2219 | likely_benign | 0.2927 | benign | -0.392 | Destabilizing | 0.978 | D | 0.575 | neutral | N | 0.45017351 | None | None | N |
| D/C | 0.6904 | likely_pathogenic | 0.7838 | pathogenic | -0.052 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/E | 0.1387 | likely_benign | 0.1707 | benign | -0.501 | Destabilizing | 0.198 | N | 0.21 | neutral | N | 0.402419635 | None | None | N |
| D/F | 0.7609 | likely_pathogenic | 0.8356 | pathogenic | -0.375 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/G | 0.2251 | likely_benign | 0.3027 | benign | -0.627 | Destabilizing | 0.989 | D | 0.593 | neutral | N | 0.485864951 | None | None | N |
| D/H | 0.3905 | ambiguous | 0.5101 | ambiguous | -0.509 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.495273868 | None | None | N |
| D/I | 0.5691 | likely_pathogenic | 0.6739 | pathogenic | 0.188 | Stabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/K | 0.4695 | ambiguous | 0.6009 | pathogenic | -0.138 | Destabilizing | 0.983 | D | 0.562 | neutral | None | None | None | None | N |
| D/L | 0.5288 | ambiguous | 0.6193 | pathogenic | 0.188 | Stabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/M | 0.7211 | likely_pathogenic | 0.8078 | pathogenic | 0.466 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/N | 0.1181 | likely_benign | 0.1554 | benign | -0.289 | Destabilizing | 0.989 | D | 0.529 | neutral | N | 0.50050633 | None | None | N |
| D/P | 0.5677 | likely_pathogenic | 0.674 | pathogenic | 0.018 | Stabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| D/Q | 0.3846 | ambiguous | 0.5001 | ambiguous | -0.251 | Destabilizing | 0.995 | D | 0.553 | neutral | None | None | None | None | N |
| D/R | 0.5314 | ambiguous | 0.6515 | pathogenic | 0.003 | Stabilizing | 0.995 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/S | 0.1293 | likely_benign | 0.1729 | benign | -0.455 | Destabilizing | 0.983 | D | 0.459 | neutral | None | None | None | None | N |
| D/T | 0.3082 | likely_benign | 0.4027 | ambiguous | -0.284 | Destabilizing | 0.998 | D | 0.636 | neutral | None | None | None | None | N |
| D/V | 0.3604 | ambiguous | 0.4488 | ambiguous | 0.018 | Stabilizing | 0.997 | D | 0.715 | prob.delet. | N | 0.518841374 | None | None | N |
| D/W | 0.9377 | likely_pathogenic | 0.9601 | pathogenic | -0.28 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| D/Y | 0.3853 | ambiguous | 0.4717 | ambiguous | -0.17 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | N | 0.497794098 | 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.