Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1129 | 3610;3611;3612 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
| N2AB | 1129 | 3610;3611;3612 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
| N2A | 1129 | 3610;3611;3612 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
| N2B | 1083 | 3472;3473;3474 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
| Novex-1 | 1083 | 3472;3473;3474 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
| Novex-2 | 1083 | 3472;3473;3474 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
| Novex-3 | 1129 | 3610;3611;3612 | chr2:178781259;178781258;178781257 | chr2:179645986;179645985;179645984 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs765840063  |
0.133 | 0.997 | N | 0.609 | 0.374 | 0.324161360171 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| K/N | rs765840063 |
0.133 | 0.997 | N | 0.609 | 0.374 | 0.324161360171 | gnomAD-4.0.0 | 3.18216E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86549E-05 | 0 |
| K/R | rs181375012 |
0.109 | 0.121 | N | 0.213 | 0.279 | None | gnomAD-2.1.1 | 2.48E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.52077E-04 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs181375012 |
0.109 | 0.121 | N | 0.213 | 0.279 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 7.6864E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs181375012 |
0.109 | 0.121 | N | 0.213 | 0.279 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| K/R | rs181375012 |
0.109 | 0.121 | N | 0.213 | 0.279 | None | gnomAD-4.0.0 | 5.45235E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.94058E-03 | None | 0 | 0 | 0 | 0 | 1.60005E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7912 | likely_pathogenic | 0.7166 | pathogenic | -0.305 | Destabilizing | 0.983 | D | 0.546 | neutral | None | None | None | None | I |
| K/C | 0.9523 | likely_pathogenic | 0.9293 | pathogenic | -0.399 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| K/D | 0.9324 | likely_pathogenic | 0.8967 | pathogenic | 0.34 | Stabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | I |
| K/E | 0.6307 | likely_pathogenic | 0.5151 | ambiguous | 0.374 | Stabilizing | 0.978 | D | 0.509 | neutral | N | 0.491486757 | None | None | I |
| K/F | 0.9706 | likely_pathogenic | 0.9616 | pathogenic | -0.482 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| K/G | 0.9071 | likely_pathogenic | 0.8782 | pathogenic | -0.552 | Destabilizing | 0.998 | D | 0.549 | neutral | None | None | None | None | I |
| K/H | 0.544 | ambiguous | 0.4881 | ambiguous | -1.009 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| K/I | 0.7495 | likely_pathogenic | 0.6829 | pathogenic | 0.28 | Stabilizing | 0.999 | D | 0.721 | prob.delet. | N | 0.510079644 | None | None | I |
| K/L | 0.786 | likely_pathogenic | 0.7256 | pathogenic | 0.28 | Stabilizing | 0.995 | D | 0.549 | neutral | None | None | None | None | I |
| K/M | 0.6359 | likely_pathogenic | 0.5393 | ambiguous | 0.288 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| K/N | 0.8388 | likely_pathogenic | 0.7787 | pathogenic | 0.158 | Stabilizing | 0.997 | D | 0.609 | neutral | N | 0.501054178 | None | None | I |
| K/P | 0.9914 | likely_pathogenic | 0.9909 | pathogenic | 0.114 | Stabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | I |
| K/Q | 0.3011 | likely_benign | 0.2423 | benign | -0.079 | Destabilizing | 0.994 | D | 0.615 | neutral | N | 0.462456593 | None | None | I |
| K/R | 0.1167 | likely_benign | 0.1136 | benign | -0.122 | Destabilizing | 0.121 | N | 0.213 | neutral | N | 0.44323686 | None | None | I |
| K/S | 0.8081 | likely_pathogenic | 0.7433 | pathogenic | -0.533 | Destabilizing | 0.992 | D | 0.567 | neutral | None | None | None | None | I |
| K/T | 0.4698 | ambiguous | 0.3734 | ambiguous | -0.326 | Destabilizing | 0.997 | D | 0.615 | neutral | N | 0.490080337 | None | None | I |
| K/V | 0.707 | likely_pathogenic | 0.6336 | pathogenic | 0.114 | Stabilizing | 0.998 | D | 0.672 | neutral | None | None | None | None | I |
| K/W | 0.9584 | likely_pathogenic | 0.9485 | pathogenic | -0.361 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| K/Y | 0.9304 | likely_pathogenic | 0.9129 | pathogenic | 0.002 | Stabilizing | 0.999 | D | 0.685 | 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.