Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1633 | 5122;5123;5124 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
| N2AB | 1633 | 5122;5123;5124 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
| N2A | 1633 | 5122;5123;5124 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
| N2B | 1587 | 4984;4985;4986 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
| Novex-1 | 1587 | 4984;4985;4986 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
| Novex-2 | 1587 | 4984;4985;4986 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
| Novex-3 | 1633 | 5122;5123;5124 | chr2:178776967;178776966;178776965 | chr2:179641694;179641693;179641692 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs1406457857  |
-1.053 | 0.993 | N | 0.256 | 0.278 | 0.618819884562 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/V | rs1406457857 |
-1.053 | 0.993 | N | 0.256 | 0.278 | 0.618819884562 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs1406457857 |
-1.053 | 0.993 | N | 0.256 | 0.278 | 0.618819884562 | gnomAD-4.0.0 | 3.84228E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17556E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9622 | likely_pathogenic | 0.9526 | pathogenic | -1.825 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | I |
| I/C | 0.99 | likely_pathogenic | 0.9847 | pathogenic | -1.086 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| I/D | 0.999 | likely_pathogenic | 0.9988 | pathogenic | -1.759 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | I |
| I/E | 0.9946 | likely_pathogenic | 0.994 | pathogenic | -1.784 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| I/F | 0.8164 | likely_pathogenic | 0.7939 | pathogenic | -1.494 | Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.509482545 | None | None | I |
| I/G | 0.9961 | likely_pathogenic | 0.9949 | pathogenic | -2.128 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| I/H | 0.9951 | likely_pathogenic | 0.9938 | pathogenic | -1.407 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| I/K | 0.9861 | likely_pathogenic | 0.984 | pathogenic | -1.265 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| I/L | 0.4963 | ambiguous | 0.4448 | ambiguous | -1.061 | Destabilizing | 0.993 | D | 0.267 | neutral | D | 0.543989889 | None | None | I |
| I/M | 0.47 | ambiguous | 0.4067 | ambiguous | -0.711 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.501245354 | None | None | I |
| I/N | 0.9842 | likely_pathogenic | 0.9812 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.852 | deleterious | N | 0.508478572 | None | None | I |
| I/P | 0.9981 | likely_pathogenic | 0.998 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| I/Q | 0.9889 | likely_pathogenic | 0.9871 | pathogenic | -1.316 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| I/R | 0.9775 | likely_pathogenic | 0.9764 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| I/S | 0.9705 | likely_pathogenic | 0.9661 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.816 | deleterious | N | 0.477021311 | None | None | I |
| I/T | 0.9397 | likely_pathogenic | 0.9234 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.449945081 | None | None | I |
| I/V | 0.18 | likely_benign | 0.1443 | benign | -1.286 | Destabilizing | 0.993 | D | 0.256 | neutral | N | 0.48545748 | None | None | I |
| I/W | 0.9904 | likely_pathogenic | 0.9898 | pathogenic | -1.567 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| I/Y | 0.9778 | likely_pathogenic | 0.9753 | pathogenic | -1.351 | Destabilizing | 1.0 | D | 0.813 | deleterious | 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.