Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28856 | 86791;86792;86793 | chr2:178559566;178559565;178559564 | chr2:179424293;179424292;179424291 |
| N2AB | 27215 | 81868;81869;81870 | chr2:178559566;178559565;178559564 | chr2:179424293;179424292;179424291 |
| N2A | 26288 | 79087;79088;79089 | chr2:178559566;178559565;178559564 | chr2:179424293;179424292;179424291 |
| N2B | 19791 | 59596;59597;59598 | chr2:178559566;178559565;178559564 | chr2:179424293;179424292;179424291 |
| Novex-1 | 19916 | 59971;59972;59973 | chr2:178559566;178559565;178559564 | chr2:179424293;179424292;179424291 |
| Novex-2 | 19983 | 60172;60173;60174 | chr2:178559566;178559565;178559564 | chr2:179424293;179424292;179424291 |
| 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/E | None | None | 0.001 | N | 0.195 | 0.155 | 0.146414634003 | gnomAD-4.0.0 | 2.05264E-06 | None | None | None | None | N | None | 0 | 4.47187E-05 | None | 0 | 0 | None | 0 | 0 | 8.99483E-07 | 0 | 0 |
| D/H | rs747235124  |
0.222 | 0.931 | N | 0.613 | 0.382 | 0.353125101423 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/H | rs747235124 |
0.222 | 0.931 | N | 0.613 | 0.382 | 0.353125101423 | gnomAD-4.0.0 | 1.59132E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85845E-06 | 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 | 0.1168 | likely_benign | 0.1017 | benign | -0.147 | Destabilizing | 0.201 | N | 0.54 | neutral | N | 0.51268898 | None | None | N |
| D/C | 0.468 | ambiguous | 0.4296 | ambiguous | 0.049 | Stabilizing | 0.982 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/E | 0.087 | likely_benign | 0.089 | benign | -0.303 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.43892194 | None | None | N |
| D/F | 0.4887 | ambiguous | 0.4364 | ambiguous | -0.128 | Destabilizing | 0.935 | D | 0.66 | neutral | None | None | None | None | N |
| D/G | 0.1321 | likely_benign | 0.1119 | benign | -0.327 | Destabilizing | 0.334 | N | 0.609 | neutral | N | 0.467925744 | None | None | N |
| D/H | 0.2052 | likely_benign | 0.1786 | benign | 0.127 | Stabilizing | 0.931 | D | 0.613 | neutral | N | 0.483943312 | None | None | N |
| D/I | 0.3168 | likely_benign | 0.2775 | benign | 0.273 | Stabilizing | 0.826 | D | 0.669 | neutral | None | None | None | None | N |
| D/K | 0.2741 | likely_benign | 0.2359 | benign | 0.417 | Stabilizing | 0.25 | N | 0.578 | neutral | None | None | None | None | N |
| D/L | 0.3163 | likely_benign | 0.2753 | benign | 0.273 | Stabilizing | 0.7 | D | 0.645 | neutral | None | None | None | None | N |
| D/M | 0.4163 | ambiguous | 0.3877 | ambiguous | 0.299 | Stabilizing | 0.982 | D | 0.643 | neutral | None | None | None | None | N |
| D/N | 0.0813 | likely_benign | 0.0751 | benign | 0.122 | Stabilizing | 0.334 | N | 0.591 | neutral | N | 0.495372656 | None | None | N |
| D/P | 0.8246 | likely_pathogenic | 0.7365 | pathogenic | 0.155 | Stabilizing | 0.826 | D | 0.615 | neutral | None | None | None | None | N |
| D/Q | 0.211 | likely_benign | 0.1937 | benign | 0.142 | Stabilizing | 0.539 | D | 0.562 | neutral | None | None | None | None | N |
| D/R | 0.3443 | ambiguous | 0.2858 | benign | 0.59 | Stabilizing | 0.539 | D | 0.605 | neutral | None | None | None | None | N |
| D/S | 0.1031 | likely_benign | 0.0943 | benign | 0.029 | Stabilizing | 0.25 | N | 0.555 | neutral | None | None | None | None | N |
| D/T | 0.1729 | likely_benign | 0.155 | benign | 0.168 | Stabilizing | 0.7 | D | 0.581 | neutral | None | None | None | None | N |
| D/V | 0.1848 | likely_benign | 0.1611 | benign | 0.155 | Stabilizing | 0.638 | D | 0.633 | neutral | N | 0.475927915 | None | None | N |
| D/W | 0.8108 | likely_pathogenic | 0.7675 | pathogenic | -0.025 | Destabilizing | 0.982 | D | 0.672 | neutral | None | None | None | None | N |
| D/Y | 0.2092 | likely_benign | 0.1769 | benign | 0.11 | Stabilizing | 0.916 | D | 0.661 | neutral | N | 0.469953661 | 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.