Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4644 | 14155;14156;14157 | chr2:178739303;178739302;178739301 | chr2:179604030;179604029;179604028 |
| N2AB | 4327 | 13204;13205;13206 | chr2:178739303;178739302;178739301 | chr2:179604030;179604029;179604028 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4281 | 13066;13067;13068 | chr2:178739303;178739302;178739301 | chr2:179604030;179604029;179604028 |
| Novex-1 | 4406 | 13441;13442;13443 | chr2:178739303;178739302;178739301 | chr2:179604030;179604029;179604028 |
| Novex-2 | 4473 | 13642;13643;13644 | chr2:178739303;178739302;178739301 | chr2:179604030;179604029;179604028 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.505 | D | 0.473 | 0.43 | None | gnomAD-4.0.0 | 1.59222E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85992E-06 | 0 | 0 |
| V/L | rs2082069274  |
None | 0.001 | N | 0.203 | 0.086 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs2082069274 |
None | 0.001 | N | 0.203 | 0.086 | None | gnomAD-4.0.0 | 6.57471E-06 | None | None | None | None | N | None | 0 | 6.55136E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs2082069274 |
None | 0.782 | N | 0.493 | 0.191 | None | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4484 | ambiguous | 0.5204 | ambiguous | -1.578 | Destabilizing | 0.505 | D | 0.473 | neutral | D | 0.566702751 | None | None | N |
| V/C | 0.8197 | likely_pathogenic | 0.8337 | pathogenic | -0.91 | Destabilizing | 0.991 | D | 0.592 | neutral | None | None | None | None | N |
| V/D | 0.9192 | likely_pathogenic | 0.9485 | pathogenic | -2.075 | Highly Destabilizing | 0.967 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/E | 0.8091 | likely_pathogenic | 0.8596 | pathogenic | -1.841 | Destabilizing | 0.879 | D | 0.657 | neutral | D | 0.556333186 | None | None | N |
| V/F | 0.304 | likely_benign | 0.3626 | ambiguous | -0.95 | Destabilizing | 0.704 | D | 0.612 | neutral | None | None | None | None | N |
| V/G | 0.6226 | likely_pathogenic | 0.7104 | pathogenic | -2.104 | Highly Destabilizing | 0.879 | D | 0.681 | prob.neutral | D | 0.651179916 | None | None | N |
| V/H | 0.8668 | likely_pathogenic | 0.9034 | pathogenic | -1.902 | Destabilizing | 0.991 | D | 0.706 | prob.neutral | None | None | None | None | N |
| V/I | 0.0845 | likely_benign | 0.0814 | benign | -0.116 | Destabilizing | 0.004 | N | 0.201 | neutral | None | None | None | None | N |
| V/K | 0.7849 | likely_pathogenic | 0.8307 | pathogenic | -1.211 | Destabilizing | 0.906 | D | 0.65 | neutral | None | None | None | None | N |
| V/L | 0.1621 | likely_benign | 0.1792 | benign | -0.116 | Destabilizing | 0.001 | N | 0.203 | neutral | N | 0.440635256 | None | None | N |
| V/M | 0.2663 | likely_benign | 0.3049 | benign | -0.105 | Destabilizing | 0.782 | D | 0.493 | neutral | N | 0.511629959 | None | None | N |
| V/N | 0.8245 | likely_pathogenic | 0.8803 | pathogenic | -1.574 | Destabilizing | 0.967 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/P | 0.8575 | likely_pathogenic | 0.9043 | pathogenic | -0.576 | Destabilizing | 0.967 | D | 0.672 | neutral | None | None | None | None | N |
| V/Q | 0.7333 | likely_pathogenic | 0.8035 | pathogenic | -1.375 | Destabilizing | 0.967 | D | 0.665 | neutral | None | None | None | None | N |
| V/R | 0.7026 | likely_pathogenic | 0.7673 | pathogenic | -1.207 | Destabilizing | 0.906 | D | 0.72 | prob.delet. | None | None | None | None | N |
| V/S | 0.6555 | likely_pathogenic | 0.7433 | pathogenic | -2.159 | Highly Destabilizing | 0.906 | D | 0.623 | neutral | None | None | None | None | N |
| V/T | 0.5958 | likely_pathogenic | 0.6774 | pathogenic | -1.772 | Destabilizing | 0.575 | D | 0.454 | neutral | None | None | None | None | N |
| V/W | 0.9118 | likely_pathogenic | 0.9329 | pathogenic | -1.482 | Destabilizing | 0.991 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/Y | 0.7691 | likely_pathogenic | 0.8159 | pathogenic | -0.995 | Destabilizing | 0.906 | D | 0.628 | 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.