Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18867 | 56824;56825;56826 | chr2:178599194;178599193;178599192 | chr2:179463921;179463920;179463919 |
| N2AB | 17226 | 51901;51902;51903 | chr2:178599194;178599193;178599192 | chr2:179463921;179463920;179463919 |
| N2A | 16299 | 49120;49121;49122 | chr2:178599194;178599193;178599192 | chr2:179463921;179463920;179463919 |
| N2B | 9802 | 29629;29630;29631 | chr2:178599194;178599193;178599192 | chr2:179463921;179463920;179463919 |
| Novex-1 | 9927 | 30004;30005;30006 | chr2:178599194;178599193;178599192 | chr2:179463921;179463920;179463919 |
| Novex-2 | 9994 | 30205;30206;30207 | chr2:178599194;178599193;178599192 | chr2:179463921;179463920;179463919 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.497 | N | 0.625 | 0.19 | 0.338834610459 | gnomAD-4.0.0 | 1.89446E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.88984E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1178126114  |
-0.865 | 0.124 | N | 0.573 | 0.216 | 0.515490261806 | gnomAD-2.1.1 | 5.75E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.75E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1178126114 |
-0.865 | 0.124 | N | 0.573 | 0.216 | 0.515490261806 | gnomAD-4.0.0 | 1.89454E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.8885E-05 | None | 0 | 0 | 0 | 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 | 0.1917 | likely_benign | 0.1931 | benign | -1.453 | Destabilizing | 0.072 | N | 0.539 | neutral | None | None | None | None | N |
| I/C | 0.6087 | likely_pathogenic | 0.5711 | pathogenic | -0.906 | Destabilizing | 0.909 | D | 0.671 | neutral | None | None | None | None | N |
| I/D | 0.6713 | likely_pathogenic | 0.6134 | pathogenic | -0.874 | Destabilizing | 0.726 | D | 0.748 | deleterious | None | None | None | None | N |
| I/E | 0.4974 | ambiguous | 0.4457 | ambiguous | -0.928 | Destabilizing | 0.726 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/F | 0.1858 | likely_benign | 0.1702 | benign | -1.182 | Destabilizing | 0.497 | N | 0.625 | neutral | N | 0.477133612 | None | None | N |
| I/G | 0.6255 | likely_pathogenic | 0.5848 | pathogenic | -1.706 | Destabilizing | 0.726 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/H | 0.5259 | ambiguous | 0.4747 | ambiguous | -0.784 | Destabilizing | 0.968 | D | 0.743 | deleterious | None | None | None | None | N |
| I/K | 0.2861 | likely_benign | 0.2443 | benign | -0.848 | Destabilizing | 0.726 | D | 0.741 | deleterious | None | None | None | None | N |
| I/L | 0.1389 | likely_benign | 0.1247 | benign | -0.862 | Destabilizing | 0.025 | N | 0.253 | neutral | N | 0.428859662 | None | None | N |
| I/M | 0.1149 | likely_benign | 0.1098 | benign | -0.631 | Destabilizing | 0.497 | N | 0.651 | neutral | N | 0.453584748 | None | None | N |
| I/N | 0.3159 | likely_benign | 0.2742 | benign | -0.609 | Destabilizing | 0.859 | D | 0.745 | deleterious | N | 0.479056409 | None | None | N |
| I/P | 0.497 | ambiguous | 0.5004 | ambiguous | -1.026 | Destabilizing | 0.726 | D | 0.75 | deleterious | None | None | None | None | N |
| I/Q | 0.4118 | ambiguous | 0.3622 | ambiguous | -0.893 | Destabilizing | 0.89 | D | 0.753 | deleterious | None | None | None | None | N |
| I/R | 0.2264 | likely_benign | 0.1911 | benign | -0.144 | Destabilizing | 0.726 | D | 0.751 | deleterious | None | None | None | None | N |
| I/S | 0.2477 | likely_benign | 0.2207 | benign | -1.187 | Destabilizing | 0.497 | N | 0.711 | prob.delet. | N | 0.448869575 | None | None | N |
| I/T | 0.0801 | likely_benign | 0.0886 | benign | -1.131 | Destabilizing | 0.124 | N | 0.573 | neutral | N | 0.428667661 | None | None | N |
| I/V | 0.0657 | likely_benign | 0.0639 | benign | -1.026 | Destabilizing | None | N | 0.208 | neutral | N | 0.361866666 | None | None | N |
| I/W | 0.7573 | likely_pathogenic | 0.7287 | pathogenic | -1.137 | Destabilizing | 0.968 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Y | 0.5319 | ambiguous | 0.4678 | ambiguous | -0.934 | Destabilizing | 0.726 | D | 0.687 | prob.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.