Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30709 | 92350;92351;92352 | chr2:178549597;178549596;178549595 | chr2:179414324;179414323;179414322 |
| N2AB | 29068 | 87427;87428;87429 | chr2:178549597;178549596;178549595 | chr2:179414324;179414323;179414322 |
| N2A | 28141 | 84646;84647;84648 | chr2:178549597;178549596;178549595 | chr2:179414324;179414323;179414322 |
| N2B | 21644 | 65155;65156;65157 | chr2:178549597;178549596;178549595 | chr2:179414324;179414323;179414322 |
| Novex-1 | 21769 | 65530;65531;65532 | chr2:178549597;178549596;178549595 | chr2:179414324;179414323;179414322 |
| Novex-2 | 21836 | 65731;65732;65733 | chr2:178549597;178549596;178549595 | chr2:179414324;179414323;179414322 |
| 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/A | rs757178111  |
0.241 | 0.518 | N | 0.528 | 0.2 | 0.31501682445 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/A | rs757178111 |
0.241 | 0.518 | N | 0.528 | 0.2 | 0.31501682445 | gnomAD-4.0.0 | 1.59256E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43357E-05 | 0 |
| D/E | None | None | 0.007 | N | 0.217 | 0.073 | 0.0551355673512 | 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 |
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 | 0.1091 | likely_benign | 0.1256 | benign | -0.133 | Destabilizing | 0.518 | D | 0.528 | neutral | N | 0.477802828 | None | None | N |
| D/C | 0.5086 | ambiguous | 0.5708 | pathogenic | -0.023 | Destabilizing | 0.996 | D | 0.697 | prob.delet. | None | None | None | None | N |
| D/E | 0.0938 | likely_benign | 0.108 | benign | -0.234 | Destabilizing | 0.007 | N | 0.217 | neutral | N | 0.360226296 | None | None | N |
| D/F | 0.4337 | ambiguous | 0.5046 | ambiguous | -0.047 | Destabilizing | 0.996 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/G | 0.1599 | likely_benign | 0.1849 | benign | -0.322 | Destabilizing | 0.682 | D | 0.647 | neutral | N | 0.461585369 | None | None | N |
| D/H | 0.2285 | likely_benign | 0.2642 | benign | 0.232 | Stabilizing | 0.983 | D | 0.663 | prob.neutral | N | 0.47959431 | None | None | N |
| D/I | 0.1934 | likely_benign | 0.2317 | benign | 0.312 | Stabilizing | 0.953 | D | 0.741 | deleterious | None | None | None | None | N |
| D/K | 0.2117 | likely_benign | 0.2473 | benign | 0.352 | Stabilizing | 0.587 | D | 0.646 | neutral | None | None | None | None | N |
| D/L | 0.2155 | likely_benign | 0.2406 | benign | 0.312 | Stabilizing | 0.909 | D | 0.727 | deleterious | None | None | None | None | N |
| D/M | 0.3692 | ambiguous | 0.4271 | ambiguous | 0.287 | Stabilizing | 0.996 | D | 0.7 | prob.delet. | None | None | None | None | N |
| D/N | 0.093 | likely_benign | 0.1072 | benign | 0.06 | Stabilizing | 0.883 | D | 0.617 | neutral | N | 0.475514671 | None | None | N |
| D/P | 0.3842 | ambiguous | 0.4165 | ambiguous | 0.185 | Stabilizing | 0.953 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/Q | 0.1996 | likely_benign | 0.234 | benign | 0.099 | Stabilizing | 0.204 | N | 0.365 | neutral | None | None | None | None | N |
| D/R | 0.2921 | likely_benign | 0.34 | ambiguous | 0.567 | Stabilizing | 0.909 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/S | 0.0978 | likely_benign | 0.1097 | benign | -0.051 | Destabilizing | 0.587 | D | 0.561 | neutral | None | None | None | None | N |
| D/T | 0.1581 | likely_benign | 0.1849 | benign | 0.098 | Stabilizing | 0.909 | D | 0.638 | neutral | None | None | None | None | N |
| D/V | 0.1168 | likely_benign | 0.1426 | benign | 0.185 | Stabilizing | 0.883 | D | 0.729 | deleterious | N | 0.472282365 | None | None | N |
| D/W | 0.8394 | likely_pathogenic | 0.8787 | pathogenic | 0.067 | Stabilizing | 0.996 | D | 0.646 | neutral | None | None | None | None | N |
| D/Y | 0.1948 | likely_benign | 0.2254 | benign | 0.192 | Stabilizing | 0.994 | D | 0.698 | prob.delet. | N | 0.4798478 | 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.