Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9534 | 28825;28826;28827 | chr2:178709719;178709718;178709717 | chr2:179574446;179574445;179574444 |
| N2AB | 9217 | 27874;27875;27876 | chr2:178709719;178709718;178709717 | chr2:179574446;179574445;179574444 |
| N2A | 8290 | 25093;25094;25095 | chr2:178709719;178709718;178709717 | chr2:179574446;179574445;179574444 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1364084001  |
None | None | None | 0.149 | 0.062 | 0.17258766438 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/L | rs1364084001 |
None | None | None | 0.149 | 0.062 | 0.17258766438 | gnomAD-4.0.0 | 6.57151E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 0 | 0 |
| I/M | None | None | 0.331 | None | 0.554 | 0.24 | 0.207176502487 | gnomAD-4.0.0 | 6.84169E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99442E-07 | 0 | 0 |
| I/T | rs1420735083 |
-2.613 | 0.22 | None | 0.546 | 0.471 | 0.717020191167 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| I/T | rs1420735083 |
-2.613 | 0.22 | None | 0.546 | 0.471 | 0.717020191167 | gnomAD-4.0.0 | 1.59106E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85799E-06 | 0 | 0 |
| I/V | None | None | None | None | 0.152 | 0.103 | 0.292062946507 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7939 | likely_pathogenic | 0.7821 | pathogenic | -2.384 | Highly Destabilizing | 0.072 | N | 0.505 | neutral | None | None | None | None | I |
| I/C | 0.8245 | likely_pathogenic | 0.8309 | pathogenic | -1.475 | Destabilizing | 0.909 | D | 0.603 | neutral | None | None | None | None | I |
| I/D | 0.9755 | likely_pathogenic | 0.9809 | pathogenic | -3.14 | Highly Destabilizing | 0.726 | D | 0.718 | prob.delet. | None | None | None | None | I |
| I/E | 0.9283 | likely_pathogenic | 0.9425 | pathogenic | -2.905 | Highly Destabilizing | 0.726 | D | 0.683 | prob.neutral | None | None | None | None | I |
| I/F | 0.2437 | likely_benign | 0.2368 | benign | -1.564 | Destabilizing | 0.396 | N | 0.527 | neutral | None | None | None | None | I |
| I/G | 0.9421 | likely_pathogenic | 0.9443 | pathogenic | -2.893 | Highly Destabilizing | 0.726 | D | 0.667 | neutral | None | None | None | None | I |
| I/H | 0.8628 | likely_pathogenic | 0.8856 | pathogenic | -2.478 | Highly Destabilizing | 0.968 | D | 0.721 | prob.delet. | None | None | None | None | I |
| I/K | 0.837 | likely_pathogenic | 0.8646 | pathogenic | -1.965 | Destabilizing | 0.667 | D | 0.675 | prob.neutral | None | None | None | None | I |
| I/L | 0.0852 | likely_benign | 0.0838 | benign | -0.901 | Destabilizing | None | N | 0.149 | neutral | None | None | None | None | I |
| I/M | 0.1086 | likely_benign | 0.1143 | benign | -0.698 | Destabilizing | 0.331 | N | 0.554 | neutral | None | None | None | None | I |
| I/N | 0.781 | likely_pathogenic | 0.8351 | pathogenic | -2.379 | Highly Destabilizing | 0.89 | D | 0.726 | prob.delet. | None | None | None | None | I |
| I/P | 0.978 | likely_pathogenic | 0.9768 | pathogenic | -1.38 | Destabilizing | 0.89 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/Q | 0.8248 | likely_pathogenic | 0.8552 | pathogenic | -2.244 | Highly Destabilizing | 0.89 | D | 0.726 | prob.delet. | None | None | None | None | I |
| I/R | 0.7764 | likely_pathogenic | 0.8119 | pathogenic | -1.709 | Destabilizing | 0.667 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/S | 0.8207 | likely_pathogenic | 0.8441 | pathogenic | -2.933 | Highly Destabilizing | 0.567 | D | 0.595 | neutral | None | None | None | None | I |
| I/T | 0.7205 | likely_pathogenic | 0.7375 | pathogenic | -2.563 | Highly Destabilizing | 0.22 | N | 0.546 | neutral | None | None | None | None | I |
| I/V | 0.1248 | likely_benign | 0.1146 | benign | -1.38 | Destabilizing | None | N | 0.152 | neutral | None | None | None | None | I |
| I/W | 0.8606 | likely_pathogenic | 0.8615 | pathogenic | -2.049 | Highly Destabilizing | 0.968 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/Y | 0.6666 | likely_pathogenic | 0.7067 | pathogenic | -1.688 | Destabilizing | 0.726 | D | 0.637 | neutral | 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.