Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31254 | 93985;93986;93987 | chr2:178547866;178547865;178547864 | chr2:179412593;179412592;179412591 |
| N2AB | 29613 | 89062;89063;89064 | chr2:178547866;178547865;178547864 | chr2:179412593;179412592;179412591 |
| N2A | 28686 | 86281;86282;86283 | chr2:178547866;178547865;178547864 | chr2:179412593;179412592;179412591 |
| N2B | 22189 | 66790;66791;66792 | chr2:178547866;178547865;178547864 | chr2:179412593;179412592;179412591 |
| Novex-1 | 22314 | 67165;67166;67167 | chr2:178547866;178547865;178547864 | chr2:179412593;179412592;179412591 |
| Novex-2 | 22381 | 67366;67367;67368 | chr2:178547866;178547865;178547864 | chr2:179412593;179412592;179412591 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1424714918  |
-0.144 | 0.016 | N | 0.169 | 0.209 | 0.467416895013 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-06 | 1.40371E-04 |
| M/I | rs1424714918 |
-0.144 | 0.016 | N | 0.169 | 0.209 | 0.467416895013 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/I | rs1424714918 |
-0.144 | 0.016 | N | 0.169 | 0.209 | 0.467416895013 | gnomAD-4.0.0 | 6.57056E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46972E-05 | 0 | 0 |
| M/L | rs759588322 |
None | 0.045 | N | 0.217 | 0.248 | 0.436025050644 | gnomAD-4.0.0 | 6.84188E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99434E-07 | 0 | 0 |
| M/V | rs759588322 |
-0.338 | 0.099 | N | 0.195 | 0.253 | 0.480046427281 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/V | rs759588322 |
-0.338 | 0.099 | N | 0.195 | 0.253 | 0.480046427281 | gnomAD-4.0.0 | 2.73675E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63725E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4869 | ambiguous | 0.589 | pathogenic | -0.838 | Destabilizing | 0.25 | N | 0.291 | neutral | None | None | None | None | N |
| M/C | 0.7178 | likely_pathogenic | 0.7518 | pathogenic | -0.762 | Destabilizing | 0.992 | D | 0.337 | neutral | None | None | None | None | N |
| M/D | 0.7466 | likely_pathogenic | 0.8071 | pathogenic | 0.152 | Stabilizing | 0.85 | D | 0.419 | neutral | None | None | None | None | N |
| M/E | 0.4753 | ambiguous | 0.5473 | ambiguous | 0.138 | Stabilizing | 0.617 | D | 0.379 | neutral | None | None | None | None | N |
| M/F | 0.3949 | ambiguous | 0.458 | ambiguous | -0.168 | Destabilizing | 0.766 | D | 0.283 | neutral | None | None | None | None | N |
| M/G | 0.5993 | likely_pathogenic | 0.7015 | pathogenic | -1.072 | Destabilizing | 0.617 | D | 0.409 | neutral | None | None | None | None | N |
| M/H | 0.4897 | ambiguous | 0.5596 | ambiguous | -0.116 | Destabilizing | 0.992 | D | 0.405 | neutral | None | None | None | None | N |
| M/I | 0.3678 | ambiguous | 0.442 | ambiguous | -0.288 | Destabilizing | 0.016 | N | 0.169 | neutral | N | 0.429161598 | None | None | N |
| M/K | 0.2319 | likely_benign | 0.2944 | benign | 0.051 | Stabilizing | 0.549 | D | 0.341 | neutral | N | 0.410034333 | None | None | N |
| M/L | 0.1467 | likely_benign | 0.1797 | benign | -0.288 | Destabilizing | 0.045 | N | 0.217 | neutral | N | 0.45942579 | None | None | N |
| M/N | 0.3931 | ambiguous | 0.4639 | ambiguous | 0.144 | Stabilizing | 0.85 | D | 0.397 | neutral | None | None | None | None | N |
| M/P | 0.897 | likely_pathogenic | 0.9386 | pathogenic | -0.442 | Destabilizing | 0.92 | D | 0.403 | neutral | None | None | None | None | N |
| M/Q | 0.2447 | likely_benign | 0.2862 | benign | 0.036 | Stabilizing | 0.92 | D | 0.294 | neutral | None | None | None | None | N |
| M/R | 0.2512 | likely_benign | 0.318 | benign | 0.565 | Stabilizing | 0.81 | D | 0.323 | neutral | N | 0.433412625 | None | None | N |
| M/S | 0.462 | ambiguous | 0.5582 | ambiguous | -0.384 | Destabilizing | 0.447 | N | 0.285 | neutral | None | None | None | None | N |
| M/T | 0.3157 | likely_benign | 0.398 | ambiguous | -0.288 | Destabilizing | 0.004 | N | 0.224 | neutral | N | 0.424697141 | None | None | N |
| M/V | 0.139 | likely_benign | 0.1694 | benign | -0.442 | Destabilizing | 0.099 | N | 0.195 | neutral | N | 0.415520297 | None | None | N |
| M/W | 0.6086 | likely_pathogenic | 0.6793 | pathogenic | -0.135 | Destabilizing | 0.992 | D | 0.371 | neutral | None | None | None | None | N |
| M/Y | 0.5155 | ambiguous | 0.5503 | ambiguous | -0.06 | Destabilizing | 0.92 | D | 0.33 | 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.