Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1352 | 4279;4280;4281 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
| N2AB | 1352 | 4279;4280;4281 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
| N2A | 1352 | 4279;4280;4281 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
| N2B | 1306 | 4141;4142;4143 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
| Novex-1 | 1306 | 4141;4142;4143 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
| Novex-2 | 1306 | 4141;4142;4143 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
| Novex-3 | 1352 | 4279;4280;4281 | chr2:178779028;178779027;178779026 | chr2:179643755;179643754;179643753 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs756380712  |
-0.561 | 0.896 | N | 0.565 | 0.488 | 0.786516960604 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| P/L | rs756380712 |
-0.561 | 0.896 | N | 0.565 | 0.488 | 0.786516960604 | gnomAD-4.0.0 | 1.59079E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85688E-06 | 0 | 0 |
| P/S | None | None | 0.211 | N | 0.295 | 0.227 | 0.286848849266 | gnomAD-4.0.0 | 6.84116E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99332E-07 | 0 | 0 |
| P/T | None | None | 0.811 | N | 0.488 | 0.279 | 0.531437074999 | gnomAD-4.0.0 | 2.05235E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.698E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2218 | likely_benign | 0.2602 | benign | -1.143 | Destabilizing | 0.046 | N | 0.259 | neutral | N | 0.482417704 | None | None | N |
| P/C | 0.9128 | likely_pathogenic | 0.9202 | pathogenic | -0.898 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| P/D | 0.7692 | likely_pathogenic | 0.8161 | pathogenic | -0.78 | Destabilizing | 0.976 | D | 0.506 | neutral | None | None | None | None | N |
| P/E | 0.6447 | likely_pathogenic | 0.7074 | pathogenic | -0.834 | Destabilizing | 0.976 | D | 0.501 | neutral | None | None | None | None | N |
| P/F | 0.9007 | likely_pathogenic | 0.9166 | pathogenic | -0.962 | Destabilizing | 0.996 | D | 0.646 | neutral | None | None | None | None | N |
| P/G | 0.577 | likely_pathogenic | 0.6376 | pathogenic | -1.386 | Destabilizing | 0.851 | D | 0.489 | neutral | None | None | None | None | N |
| P/H | 0.5346 | ambiguous | 0.5907 | pathogenic | -0.816 | Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.48972235 | None | None | N |
| P/I | 0.828 | likely_pathogenic | 0.8555 | pathogenic | -0.61 | Destabilizing | 0.988 | D | 0.636 | neutral | None | None | None | None | N |
| P/K | 0.7456 | likely_pathogenic | 0.8003 | pathogenic | -0.977 | Destabilizing | 0.976 | D | 0.518 | neutral | None | None | None | None | N |
| P/L | 0.4378 | ambiguous | 0.4839 | ambiguous | -0.61 | Destabilizing | 0.896 | D | 0.565 | neutral | N | 0.485101768 | None | None | N |
| P/M | 0.7652 | likely_pathogenic | 0.8106 | pathogenic | -0.531 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| P/N | 0.6318 | likely_pathogenic | 0.6832 | pathogenic | -0.723 | Destabilizing | 0.976 | D | 0.595 | neutral | None | None | None | None | N |
| P/Q | 0.4425 | ambiguous | 0.5162 | ambiguous | -0.952 | Destabilizing | 0.988 | D | 0.596 | neutral | None | None | None | None | N |
| P/R | 0.5459 | ambiguous | 0.6128 | pathogenic | -0.394 | Destabilizing | 0.968 | D | 0.595 | neutral | N | 0.435066238 | None | None | N |
| P/S | 0.2858 | likely_benign | 0.3372 | benign | -1.209 | Destabilizing | 0.211 | N | 0.295 | neutral | N | 0.421024258 | None | None | N |
| P/T | 0.344 | ambiguous | 0.3983 | ambiguous | -1.16 | Destabilizing | 0.811 | D | 0.488 | neutral | N | 0.470180459 | None | None | N |
| P/V | 0.6687 | likely_pathogenic | 0.7188 | pathogenic | -0.751 | Destabilizing | 0.919 | D | 0.519 | neutral | None | None | None | None | N |
| P/W | 0.9471 | likely_pathogenic | 0.9567 | pathogenic | -1.048 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| P/Y | 0.8827 | likely_pathogenic | 0.9024 | pathogenic | -0.784 | Destabilizing | 0.996 | D | 0.649 | 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.