Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14099 | 42520;42521;42522 | chr2:178634486;178634485;178634484 | chr2:179499213;179499212;179499211 |
| N2AB | 12458 | 37597;37598;37599 | chr2:178634486;178634485;178634484 | chr2:179499213;179499212;179499211 |
| N2A | 11531 | 34816;34817;34818 | chr2:178634486;178634485;178634484 | chr2:179499213;179499212;179499211 |
| N2B | 5034 | 15325;15326;15327 | chr2:178634486;178634485;178634484 | chr2:179499213;179499212;179499211 |
| Novex-1 | 5159 | 15700;15701;15702 | chr2:178634486;178634485;178634484 | chr2:179499213;179499212;179499211 |
| Novex-2 | 5226 | 15901;15902;15903 | chr2:178634486;178634485;178634484 | chr2:179499213;179499212;179499211 |
| 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/G | rs1295172213  |
None | 0.989 | N | 0.471 | 0.372 | 0.332902724076 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs1295172213 |
None | 0.989 | N | 0.471 | 0.372 | 0.332902724076 | gnomAD-4.0.0 | 3.7194E-06 | None | None | None | None | N | None | 1.33601E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39117E-06 | 0 | 1.6021E-05 |
| D/H | None | None | 1.0 | N | 0.641 | 0.337 | 0.348101942276 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs1041549928 |
None | 0.998 | N | 0.527 | 0.305 | 0.312001716656 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1041549928 |
None | 0.998 | N | 0.527 | 0.305 | 0.312001716656 | gnomAD-4.0.0 | 4.06037E-06 | None | None | None | None | N | None | 3.49638E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40995E-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 | 0.3255 | likely_benign | 0.3884 | ambiguous | -0.801 | Destabilizing | 0.543 | D | 0.331 | neutral | N | 0.499873248 | None | None | N |
| D/C | 0.8592 | likely_pathogenic | 0.8956 | pathogenic | -0.209 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/E | 0.3229 | likely_benign | 0.3422 | ambiguous | -0.595 | Destabilizing | 0.543 | D | 0.231 | neutral | N | 0.374161391 | None | None | N |
| D/F | 0.8441 | likely_pathogenic | 0.887 | pathogenic | -0.642 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/G | 0.4349 | ambiguous | 0.5108 | ambiguous | -1.095 | Destabilizing | 0.989 | D | 0.471 | neutral | N | 0.51051451 | None | None | N |
| D/H | 0.4021 | ambiguous | 0.4427 | ambiguous | -0.884 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.492659572 | None | None | N |
| D/I | 0.6324 | likely_pathogenic | 0.6859 | pathogenic | -0.032 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | None | None | None | None | N |
| D/K | 0.655 | likely_pathogenic | 0.6919 | pathogenic | -0.102 | Destabilizing | 0.998 | D | 0.601 | neutral | None | None | None | None | N |
| D/L | 0.6808 | likely_pathogenic | 0.7318 | pathogenic | -0.032 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/M | 0.8436 | likely_pathogenic | 0.8721 | pathogenic | 0.442 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/N | 0.1628 | likely_benign | 0.1904 | benign | -0.504 | Destabilizing | 0.998 | D | 0.527 | neutral | N | 0.496905457 | None | None | N |
| D/P | 0.9833 | likely_pathogenic | 0.9886 | pathogenic | -0.266 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/Q | 0.5305 | ambiguous | 0.554 | ambiguous | -0.438 | Destabilizing | 0.998 | D | 0.609 | neutral | None | None | None | None | N |
| D/R | 0.6205 | likely_pathogenic | 0.6702 | pathogenic | -0.071 | Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/S | 0.2196 | likely_benign | 0.2471 | benign | -0.746 | Destabilizing | 0.983 | D | 0.406 | neutral | None | None | None | None | N |
| D/T | 0.4171 | ambiguous | 0.4496 | ambiguous | -0.493 | Destabilizing | 0.998 | D | 0.603 | neutral | None | None | None | None | N |
| D/V | 0.4338 | ambiguous | 0.5108 | ambiguous | -0.266 | Destabilizing | 0.997 | D | 0.69 | prob.neutral | N | 0.493720086 | None | None | N |
| D/W | 0.9588 | likely_pathogenic | 0.9695 | pathogenic | -0.433 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4284 | ambiguous | 0.5169 | ambiguous | -0.371 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | D | 0.560343676 | 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.