Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
| N2AB | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
| N2A | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
| N2B | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
| Novex-1 | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
| Novex-2 | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
| Novex-3 | 29 | 310;311;312 | chr2:178804558;178804557;178804556 | chr2:179669285;179669284;179669283 |
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 | 0.771 | N | 0.765 | 0.414 | 0.32714864917 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | -1.048(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79873E-06 | 0 | 0 |
| I/V | rs1458992819  |
-1.367 | None | N | 0.243 | 0.18 | 0.144782658237 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | -0.801(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| I/V | rs1458992819 |
-1.367 | None | N | 0.243 | 0.18 | 0.144782658237 | gnomAD-4.0.0 | 3.42086E-06 | None | None | None | -0.801(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 3.74434E-05 | 0 | 1.79873E-06 | 1.16042E-05 | 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 | 0.9226 | likely_pathogenic | 0.88 | pathogenic | -2.426 | Highly Destabilizing | 0.398 | N | 0.699 | prob.neutral | None | None | None | -0.518(TCAP) | N |
| I/C | 0.9657 | likely_pathogenic | 0.9489 | pathogenic | -1.99 | Destabilizing | 0.988 | D | 0.79 | deleterious | None | None | None | -0.684(TCAP) | N |
| I/D | 0.9984 | likely_pathogenic | 0.997 | pathogenic | -2.272 | Highly Destabilizing | 0.958 | D | 0.866 | deleterious | None | None | None | -0.305(TCAP) | N |
| I/E | 0.995 | likely_pathogenic | 0.9922 | pathogenic | -2.009 | Highly Destabilizing | 0.944 | D | 0.855 | deleterious | None | None | None | -0.453(TCAP) | N |
| I/F | 0.7372 | likely_pathogenic | 0.6049 | pathogenic | -1.398 | Destabilizing | 0.771 | D | 0.765 | deleterious | N | 0.520472748 | None | -1.048(TCAP) | N |
| I/G | 0.9899 | likely_pathogenic | 0.9812 | pathogenic | -3.013 | Highly Destabilizing | 0.958 | D | 0.834 | deleterious | None | None | None | -0.386(TCAP) | N |
| I/H | 0.9934 | likely_pathogenic | 0.9881 | pathogenic | -2.456 | Highly Destabilizing | 0.991 | D | 0.855 | deleterious | None | None | None | -0.029(TCAP) | N |
| I/K | 0.9918 | likely_pathogenic | 0.987 | pathogenic | -1.58 | Destabilizing | 0.401 | N | 0.856 | deleterious | None | None | None | -0.713(TCAP) | N |
| I/L | 0.3066 | likely_benign | 0.2358 | benign | -0.713 | Destabilizing | 0.006 | N | 0.423 | neutral | N | 0.501056338 | None | -0.949(TCAP) | N |
| I/M | 0.4953 | ambiguous | 0.4064 | ambiguous | -0.944 | Destabilizing | 0.503 | D | 0.723 | prob.delet. | D | 0.650997072 | None | -0.977(TCAP) | N |
| I/N | 0.9808 | likely_pathogenic | 0.9695 | pathogenic | -1.975 | Destabilizing | 0.981 | D | 0.866 | deleterious | D | 0.690597404 | None | -0.581(TCAP) | N |
| I/P | 0.9947 | likely_pathogenic | 0.9912 | pathogenic | -1.267 | Destabilizing | 0.986 | D | 0.865 | deleterious | None | None | None | -0.801(TCAP) | N |
| I/Q | 0.9897 | likely_pathogenic | 0.9847 | pathogenic | -1.752 | Destabilizing | 0.966 | D | 0.863 | deleterious | None | None | None | -0.639(TCAP) | N |
| I/R | 0.9855 | likely_pathogenic | 0.9765 | pathogenic | -1.523 | Destabilizing | 0.9 | D | 0.865 | deleterious | None | None | None | -0.746(TCAP) | N |
| I/S | 0.9554 | likely_pathogenic | 0.9324 | pathogenic | -2.801 | Highly Destabilizing | 0.894 | D | 0.818 | deleterious | D | 0.551168922 | None | -0.208(TCAP) | N |
| I/T | 0.9039 | likely_pathogenic | 0.8595 | pathogenic | -2.369 | Highly Destabilizing | 0.266 | N | 0.737 | prob.delet. | N | 0.520591331 | None | -0.385(TCAP) | N |
| I/V | 0.0932 | likely_benign | 0.085 | benign | -1.267 | Destabilizing | None | N | 0.243 | neutral | N | 0.382609749 | None | -0.801(TCAP) | N |
| I/W | 0.9957 | likely_pathogenic | 0.9931 | pathogenic | -1.671 | Destabilizing | 0.997 | D | 0.85 | deleterious | None | None | None | -1.34(TCAP) | N |
| I/Y | 0.9745 | likely_pathogenic | 0.952 | pathogenic | -1.406 | Destabilizing | 0.514 | D | 0.813 | deleterious | None | None | None | -1.114(TCAP) | 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.