Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19462 | 58609;58610;58611 | chr2:178594009;178594008;178594007 | chr2:179458736;179458735;179458734 |
| N2AB | 17821 | 53686;53687;53688 | chr2:178594009;178594008;178594007 | chr2:179458736;179458735;179458734 |
| N2A | 16894 | 50905;50906;50907 | chr2:178594009;178594008;178594007 | chr2:179458736;179458735;179458734 |
| N2B | 10397 | 31414;31415;31416 | chr2:178594009;178594008;178594007 | chr2:179458736;179458735;179458734 |
| Novex-1 | 10522 | 31789;31790;31791 | chr2:178594009;178594008;178594007 | chr2:179458736;179458735;179458734 |
| Novex-2 | 10589 | 31990;31991;31992 | chr2:178594009;178594008;178594007 | chr2:179458736;179458735;179458734 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | None | None | 0.999 | N | 0.707 | 0.445 | 0.468669884856 | gnomAD-4.0.0 | 6.84284E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99543E-07 | 0 | 0 |
| E/Q | None | None | 1.0 | N | 0.651 | 0.312 | 0.445210270852 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85904E-06 | 0 | 0 |
| E/V | rs781204863  |
-0.085 | 1.0 | D | 0.749 | 0.515 | 0.49908893446 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.28E-05 | 1.78E-05 | 0 |
| E/V | rs781204863 |
-0.085 | 1.0 | D | 0.749 | 0.515 | 0.49908893446 | gnomAD-4.0.0 | 6.15855E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 5.61777E-05 | 0 | 2.69863E-06 | 0 | 4.97051E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2594 | likely_benign | 0.2636 | benign | -0.678 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | N | 0.483592869 | None | None | I |
| E/C | 0.8967 | likely_pathogenic | 0.9058 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| E/D | 0.2829 | likely_benign | 0.2853 | benign | -0.78 | Destabilizing | 0.999 | D | 0.513 | neutral | N | 0.495963133 | None | None | I |
| E/F | 0.9028 | likely_pathogenic | 0.91 | pathogenic | -0.703 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| E/G | 0.3166 | likely_benign | 0.3295 | benign | -0.939 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.499686116 | None | None | I |
| E/H | 0.5859 | likely_pathogenic | 0.6229 | pathogenic | -0.967 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| E/I | 0.5827 | likely_pathogenic | 0.5942 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| E/K | 0.2062 | likely_benign | 0.2293 | benign | -0.058 | Destabilizing | 0.999 | D | 0.672 | neutral | N | 0.479435703 | None | None | I |
| E/L | 0.666 | likely_pathogenic | 0.682 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| E/M | 0.6297 | likely_pathogenic | 0.6391 | pathogenic | 0.438 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| E/N | 0.4361 | ambiguous | 0.4396 | ambiguous | -0.339 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| E/P | 0.9887 | likely_pathogenic | 0.9913 | pathogenic | -0.206 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| E/Q | 0.1414 | likely_benign | 0.1517 | benign | -0.306 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.518706167 | None | None | I |
| E/R | 0.3485 | ambiguous | 0.4002 | ambiguous | -0.042 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| E/S | 0.2605 | likely_benign | 0.2677 | benign | -0.573 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | I |
| E/T | 0.2331 | likely_benign | 0.239 | benign | -0.358 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| E/V | 0.3531 | ambiguous | 0.3525 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.525517496 | None | None | I |
| E/W | 0.9477 | likely_pathogenic | 0.9592 | pathogenic | -0.585 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| E/Y | 0.8234 | likely_pathogenic | 0.8432 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
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.