Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33732 | 101419;101420;101421 | chr2:178535421;178535420;178535419 | chr2:179400148;179400147;179400146 |
| N2AB | 32091 | 96496;96497;96498 | chr2:178535421;178535420;178535419 | chr2:179400148;179400147;179400146 |
| N2A | 31164 | 93715;93716;93717 | chr2:178535421;178535420;178535419 | chr2:179400148;179400147;179400146 |
| N2B | 24667 | 74224;74225;74226 | chr2:178535421;178535420;178535419 | chr2:179400148;179400147;179400146 |
| Novex-1 | 24792 | 74599;74600;74601 | chr2:178535421;178535420;178535419 | chr2:179400148;179400147;179400146 |
| Novex-2 | 24859 | 74800;74801;74802 | chr2:178535421;178535420;178535419 | chr2:179400148;179400147;179400146 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1690986189  |
None | 0.499 | N | 0.475 | 0.213 | 0.143124449307 | 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 |
| T/I | rs1690985152 |
None | 0.998 | N | 0.575 | 0.389 | 0.48418289745800003 | 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 |
| T/I | rs1690985152 |
None | 0.998 | N | 0.575 | 0.389 | 0.48418289745800003 | gnomAD-4.0.0 | 2.56187E-06 | None | None | None | None | N | None | 1.69096E-05 | 1.69463E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1953 | likely_benign | 0.1236 | benign | -0.245 | Destabilizing | 0.499 | N | 0.475 | neutral | N | 0.472631869 | None | None | N |
| T/C | 0.8799 | likely_pathogenic | 0.7816 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.6 | neutral | None | None | None | None | N |
| T/D | 0.7844 | likely_pathogenic | 0.5272 | ambiguous | -0.213 | Destabilizing | 0.986 | D | 0.532 | neutral | None | None | None | None | N |
| T/E | 0.8052 | likely_pathogenic | 0.5626 | ambiguous | -0.309 | Destabilizing | 0.996 | D | 0.513 | neutral | None | None | None | None | N |
| T/F | 0.818 | likely_pathogenic | 0.6595 | pathogenic | -0.931 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| T/G | 0.3807 | ambiguous | 0.2603 | benign | -0.265 | Destabilizing | 0.994 | D | 0.457 | neutral | None | None | None | None | N |
| T/H | 0.7298 | likely_pathogenic | 0.509 | ambiguous | -0.414 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| T/I | 0.7694 | likely_pathogenic | 0.6008 | pathogenic | -0.304 | Destabilizing | 0.998 | D | 0.575 | neutral | N | 0.466786882 | None | None | N |
| T/K | 0.7347 | likely_pathogenic | 0.486 | ambiguous | -0.38 | Destabilizing | 0.997 | D | 0.53 | neutral | None | None | None | None | N |
| T/L | 0.475 | ambiguous | 0.3264 | benign | -0.304 | Destabilizing | 0.995 | D | 0.493 | neutral | None | None | None | None | N |
| T/M | 0.3445 | ambiguous | 0.2332 | benign | -0.266 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| T/N | 0.3665 | ambiguous | 0.2092 | benign | -0.211 | Destabilizing | 0.981 | D | 0.519 | neutral | N | 0.475802673 | None | None | N |
| T/P | 0.4548 | ambiguous | 0.3036 | benign | -0.265 | Destabilizing | 0.991 | D | 0.569 | neutral | N | 0.46938092 | None | None | N |
| T/Q | 0.6604 | likely_pathogenic | 0.4466 | ambiguous | -0.411 | Destabilizing | 0.997 | D | 0.575 | neutral | None | None | None | None | N |
| T/R | 0.7053 | likely_pathogenic | 0.4449 | ambiguous | -0.121 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | N |
| T/S | 0.216 | likely_benign | 0.1452 | benign | -0.353 | Destabilizing | 0.158 | N | 0.357 | neutral | N | 0.42454992 | None | None | N |
| T/V | 0.5555 | ambiguous | 0.4074 | ambiguous | -0.265 | Destabilizing | 0.993 | D | 0.479 | neutral | None | None | None | None | N |
| T/W | 0.9557 | likely_pathogenic | 0.902 | pathogenic | -1.022 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/Y | 0.8522 | likely_pathogenic | 0.6605 | pathogenic | -0.717 | Destabilizing | 1.0 | D | 0.627 | 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.