Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17714 | 53365;53366;53367 | chr2:178607548;178607547;178607546 | chr2:179472275;179472274;179472273 |
| N2AB | 16073 | 48442;48443;48444 | chr2:178607548;178607547;178607546 | chr2:179472275;179472274;179472273 |
| N2A | 15146 | 45661;45662;45663 | chr2:178607548;178607547;178607546 | chr2:179472275;179472274;179472273 |
| N2B | 8649 | 26170;26171;26172 | chr2:178607548;178607547;178607546 | chr2:179472275;179472274;179472273 |
| Novex-1 | 8774 | 26545;26546;26547 | chr2:178607548;178607547;178607546 | chr2:179472275;179472274;179472273 |
| Novex-2 | 8841 | 26746;26747;26748 | chr2:178607548;178607547;178607546 | chr2:179472275;179472274;179472273 |
| 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/N | None | None | 0.046 | N | 0.305 | 0.189 | 0.216624796971 | gnomAD-4.0.0 | 6.84404E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15953E-05 | 0 |
| D/Y | rs1051253179  |
0.225 | 0.999 | N | 0.666 | 0.43 | 0.748738615344 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| D/Y | rs1051253179 |
0.225 | 0.999 | N | 0.666 | 0.43 | 0.748738615344 | gnomAD-4.0.0 | 1.23193E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61948E-05 | 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 | 0.1586 | likely_benign | 0.1643 | benign | -0.182 | Destabilizing | 0.939 | D | 0.525 | neutral | D | 0.529651093 | None | None | N |
| D/C | 0.4968 | ambiguous | 0.5566 | ambiguous | -0.005 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| D/E | 0.1576 | likely_benign | 0.1628 | benign | -0.291 | Destabilizing | 0.17 | N | 0.355 | neutral | N | 0.492402213 | None | None | N |
| D/F | 0.5685 | likely_pathogenic | 0.6452 | pathogenic | 0.044 | Stabilizing | 0.999 | D | 0.666 | neutral | None | None | None | None | N |
| D/G | 0.1844 | likely_benign | 0.2159 | benign | -0.431 | Destabilizing | 0.885 | D | 0.559 | neutral | N | 0.485123352 | None | None | N |
| D/H | 0.2874 | likely_benign | 0.3269 | benign | 0.093 | Stabilizing | 0.998 | D | 0.565 | neutral | N | 0.492529638 | None | None | N |
| D/I | 0.3011 | likely_benign | 0.3637 | ambiguous | 0.436 | Stabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/K | 0.4181 | ambiguous | 0.4922 | ambiguous | 0.241 | Stabilizing | 0.953 | D | 0.537 | neutral | None | None | None | None | N |
| D/L | 0.2878 | likely_benign | 0.3354 | benign | 0.436 | Stabilizing | 0.993 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/M | 0.5779 | likely_pathogenic | 0.6247 | pathogenic | 0.52 | Stabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| D/N | 0.1138 | likely_benign | 0.1154 | benign | -0.146 | Destabilizing | 0.046 | N | 0.305 | neutral | N | 0.511988052 | None | None | N |
| D/P | 0.394 | ambiguous | 0.4253 | ambiguous | 0.254 | Stabilizing | 0.998 | D | 0.576 | neutral | None | None | None | None | N |
| D/Q | 0.2926 | likely_benign | 0.3259 | benign | -0.06 | Destabilizing | 0.986 | D | 0.51 | neutral | None | None | None | None | N |
| D/R | 0.4322 | ambiguous | 0.5084 | ambiguous | 0.433 | Stabilizing | 0.986 | D | 0.637 | neutral | None | None | None | None | N |
| D/S | 0.1467 | likely_benign | 0.1472 | benign | -0.267 | Destabilizing | 0.91 | D | 0.5 | neutral | None | None | None | None | N |
| D/T | 0.287 | likely_benign | 0.3177 | benign | -0.067 | Destabilizing | 0.986 | D | 0.524 | neutral | None | None | None | None | N |
| D/V | 0.1721 | likely_benign | 0.1985 | benign | 0.254 | Stabilizing | 0.991 | D | 0.691 | prob.neutral | N | 0.486858099 | None | None | N |
| D/W | 0.8205 | likely_pathogenic | 0.8748 | pathogenic | 0.187 | Stabilizing | 0.999 | D | 0.676 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2227 | likely_benign | 0.2898 | benign | 0.285 | Stabilizing | 0.999 | D | 0.666 | neutral | N | 0.502506818 | 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.