Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29643 | 89152;89153;89154 | chr2:178554184;178554183;178554182 | chr2:179418911;179418910;179418909 |
| N2AB | 28002 | 84229;84230;84231 | chr2:178554184;178554183;178554182 | chr2:179418911;179418910;179418909 |
| N2A | 27075 | 81448;81449;81450 | chr2:178554184;178554183;178554182 | chr2:179418911;179418910;179418909 |
| N2B | 20578 | 61957;61958;61959 | chr2:178554184;178554183;178554182 | chr2:179418911;179418910;179418909 |
| Novex-1 | 20703 | 62332;62333;62334 | chr2:178554184;178554183;178554182 | chr2:179418911;179418910;179418909 |
| Novex-2 | 20770 | 62533;62534;62535 | chr2:178554184;178554183;178554182 | chr2:179418911;179418910;179418909 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.046 | D | 0.227 | 0.131 | 0.167679373172 | gnomAD-4.0.0 | 1.60337E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77562E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | rs1307408186  |
-0.766 | 0.982 | N | 0.597 | 0.35 | 0.473616572423 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.43E-05 | None | 0 | 0 | 0 |
| T/K | rs1307408186 |
-0.766 | 0.982 | N | 0.597 | 0.35 | 0.473616572423 | gnomAD-4.0.0 | 4.81084E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.3811E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1436 | likely_benign | 0.1647 | benign | -0.688 | Destabilizing | 0.046 | N | 0.227 | neutral | D | 0.524735557 | None | None | N |
| T/C | 0.5403 | ambiguous | 0.5669 | pathogenic | -0.424 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| T/D | 0.5703 | likely_pathogenic | 0.6212 | pathogenic | 0.074 | Stabilizing | 0.986 | D | 0.583 | neutral | None | None | None | None | N |
| T/E | 0.4625 | ambiguous | 0.4814 | ambiguous | 0.09 | Stabilizing | 0.986 | D | 0.592 | neutral | None | None | None | None | N |
| T/F | 0.4514 | ambiguous | 0.5119 | ambiguous | -0.753 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/G | 0.2937 | likely_benign | 0.3519 | ambiguous | -0.954 | Destabilizing | 0.91 | D | 0.577 | neutral | None | None | None | None | N |
| T/H | 0.4384 | ambiguous | 0.5021 | ambiguous | -1.148 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| T/I | 0.3819 | ambiguous | 0.3779 | ambiguous | -0.073 | Destabilizing | 0.982 | D | 0.635 | neutral | N | 0.521156535 | None | None | N |
| T/K | 0.4193 | ambiguous | 0.4618 | ambiguous | -0.602 | Destabilizing | 0.982 | D | 0.597 | neutral | N | 0.517500154 | None | None | N |
| T/L | 0.1646 | likely_benign | 0.1801 | benign | -0.073 | Destabilizing | 0.953 | D | 0.551 | neutral | None | None | None | None | N |
| T/M | 0.1322 | likely_benign | 0.145 | benign | 0.019 | Stabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| T/N | 0.1797 | likely_benign | 0.2188 | benign | -0.581 | Destabilizing | 0.986 | D | 0.589 | neutral | None | None | None | None | N |
| T/P | 0.6052 | likely_pathogenic | 0.6397 | pathogenic | -0.244 | Destabilizing | 0.991 | D | 0.649 | neutral | N | 0.486527433 | None | None | N |
| T/Q | 0.335 | likely_benign | 0.3802 | ambiguous | -0.646 | Destabilizing | 0.993 | D | 0.663 | neutral | None | None | None | None | N |
| T/R | 0.3667 | ambiguous | 0.4261 | ambiguous | -0.43 | Destabilizing | 0.982 | D | 0.663 | neutral | N | 0.477017552 | None | None | N |
| T/S | 0.1251 | likely_benign | 0.1512 | benign | -0.869 | Destabilizing | 0.17 | N | 0.296 | neutral | N | 0.449522936 | None | None | N |
| T/V | 0.2666 | likely_benign | 0.2593 | benign | -0.244 | Destabilizing | 0.91 | D | 0.542 | neutral | None | None | None | None | N |
| T/W | 0.7862 | likely_pathogenic | 0.8215 | pathogenic | -0.743 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/Y | 0.5072 | ambiguous | 0.5682 | pathogenic | -0.485 | Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | 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.