Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34198 | 102817;102818;102819 | chr2:178534023;178534022;178534021 | chr2:179398750;179398749;179398748 |
| N2AB | 32557 | 97894;97895;97896 | chr2:178534023;178534022;178534021 | chr2:179398750;179398749;179398748 |
| N2A | 31630 | 95113;95114;95115 | chr2:178534023;178534022;178534021 | chr2:179398750;179398749;179398748 |
| N2B | 25133 | 75622;75623;75624 | chr2:178534023;178534022;178534021 | chr2:179398750;179398749;179398748 |
| Novex-1 | 25258 | 75997;75998;75999 | chr2:178534023;178534022;178534021 | chr2:179398750;179398749;179398748 |
| Novex-2 | 25325 | 76198;76199;76200 | chr2:178534023;178534022;178534021 | chr2:179398750;179398749;179398748 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs778876835  |
-0.049 | 0.999 | N | 0.474 | 0.152 | 0.21737058555 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| D/H | rs948836784 |
None | 1.0 | N | 0.764 | 0.298 | 0.215109475489 | 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 |
| D/H | rs948836784 |
None | 1.0 | N | 0.764 | 0.298 | 0.215109475489 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 6.54965E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs948836784 |
None | 0.999 | N | 0.709 | 0.217 | 0.141422826196 | gnomAD-4.0.0 | 3.182E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71533E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3464 | ambiguous | 0.3982 | ambiguous | -0.541 | Destabilizing | 0.984 | D | 0.634 | neutral | N | 0.463694594 | None | None | N |
| D/C | 0.8343 | likely_pathogenic | 0.8814 | pathogenic | -0.157 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| D/E | 0.2597 | likely_benign | 0.2882 | benign | -0.569 | Destabilizing | 0.999 | D | 0.474 | neutral | N | 0.456093831 | None | None | N |
| D/F | 0.8385 | likely_pathogenic | 0.8511 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| D/G | 0.1693 | likely_benign | 0.1937 | benign | -0.815 | Destabilizing | 0.275 | N | 0.369 | neutral | N | 0.475026308 | None | None | N |
| D/H | 0.4195 | ambiguous | 0.4001 | ambiguous | -0.593 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.482800429 | None | None | N |
| D/I | 0.795 | likely_pathogenic | 0.8519 | pathogenic | 0.158 | Stabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| D/K | 0.5106 | ambiguous | 0.5445 | ambiguous | -0.278 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| D/L | 0.715 | likely_pathogenic | 0.7409 | pathogenic | 0.158 | Stabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | N |
| D/M | 0.8541 | likely_pathogenic | 0.8815 | pathogenic | 0.523 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| D/N | 0.1087 | likely_benign | 0.1146 | benign | -0.559 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.41795673 | None | None | N |
| D/P | 0.9155 | likely_pathogenic | 0.9365 | pathogenic | -0.051 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| D/Q | 0.4942 | ambiguous | 0.5053 | ambiguous | -0.487 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/R | 0.553 | ambiguous | 0.5853 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| D/S | 0.2122 | likely_benign | 0.2362 | benign | -0.744 | Destabilizing | 0.994 | D | 0.643 | neutral | None | None | None | None | N |
| D/T | 0.5157 | ambiguous | 0.5756 | pathogenic | -0.535 | Destabilizing | 0.999 | D | 0.782 | deleterious | None | None | None | None | N |
| D/V | 0.5835 | likely_pathogenic | 0.6642 | pathogenic | -0.051 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.465722201 | None | None | N |
| D/W | 0.9508 | likely_pathogenic | 0.9585 | pathogenic | -0.252 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| D/Y | 0.3732 | ambiguous | 0.3983 | ambiguous | -0.18 | Destabilizing | 1.0 | D | 0.799 | deleterious | N | 0.498057883 | 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.