Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16751 | 50476;50477;50478 | chr2:178612160;178612159;178612158 | chr2:179476887;179476886;179476885 |
| N2AB | 15110 | 45553;45554;45555 | chr2:178612160;178612159;178612158 | chr2:179476887;179476886;179476885 |
| N2A | 14183 | 42772;42773;42774 | chr2:178612160;178612159;178612158 | chr2:179476887;179476886;179476885 |
| N2B | 7686 | 23281;23282;23283 | chr2:178612160;178612159;178612158 | chr2:179476887;179476886;179476885 |
| Novex-1 | 7811 | 23656;23657;23658 | chr2:178612160;178612159;178612158 | chr2:179476887;179476886;179476885 |
| Novex-2 | 7878 | 23857;23858;23859 | chr2:178612160;178612159;178612158 | chr2:179476887;179476886;179476885 |
| 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 | None | None | 0.603 | N | 0.155 | 0.185 | 0.188950314367 | gnomAD-4.0.0 | 1.60682E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87497E-06 | 0 | 0 |
| T/I | rs1440277025  |
None | 0.999 | N | 0.675 | 0.365 | 0.337868961071 | gnomAD-4.0.0 | 2.06004E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70284E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.144 | likely_benign | 0.1677 | benign | -0.628 | Destabilizing | 0.603 | D | 0.155 | neutral | N | 0.454782998 | None | None | I |
| T/C | 0.7041 | likely_pathogenic | 0.736 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| T/D | 0.8961 | likely_pathogenic | 0.9302 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.654 | prob.neutral | None | None | None | None | I |
| T/E | 0.7732 | likely_pathogenic | 0.8471 | pathogenic | -0.348 | Destabilizing | 0.999 | D | 0.622 | neutral | None | None | None | None | I |
| T/F | 0.6592 | likely_pathogenic | 0.7732 | pathogenic | -1.164 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| T/G | 0.6965 | likely_pathogenic | 0.7718 | pathogenic | -0.753 | Destabilizing | 0.993 | D | 0.591 | neutral | None | None | None | None | I |
| T/H | 0.7054 | likely_pathogenic | 0.7813 | pathogenic | -1.162 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| T/I | 0.3175 | likely_benign | 0.4132 | ambiguous | -0.408 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | N | 0.470765548 | None | None | I |
| T/K | 0.6507 | likely_pathogenic | 0.7135 | pathogenic | -0.448 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | I |
| T/L | 0.216 | likely_benign | 0.2767 | benign | -0.408 | Destabilizing | 0.993 | D | 0.586 | neutral | None | None | None | None | I |
| T/M | 0.1787 | likely_benign | 0.2356 | benign | 0.116 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| T/N | 0.4324 | ambiguous | 0.526 | ambiguous | -0.212 | Destabilizing | 1.0 | D | 0.628 | neutral | N | 0.49521834 | None | None | I |
| T/P | 0.3549 | ambiguous | 0.2769 | benign | -0.455 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.401412642 | None | None | I |
| T/Q | 0.5557 | ambiguous | 0.6336 | pathogenic | -0.575 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| T/R | 0.6154 | likely_pathogenic | 0.6878 | pathogenic | -0.097 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | I |
| T/S | 0.2915 | likely_benign | 0.35 | ambiguous | -0.415 | Destabilizing | 0.983 | D | 0.355 | neutral | N | 0.466595553 | None | None | I |
| T/V | 0.1912 | likely_benign | 0.2349 | benign | -0.455 | Destabilizing | 0.993 | D | 0.457 | neutral | None | None | None | None | I |
| T/W | 0.9446 | likely_pathogenic | 0.9639 | pathogenic | -1.095 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| T/Y | 0.7551 | likely_pathogenic | 0.8264 | pathogenic | -0.835 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
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.