Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14268 | 43027;43028;43029 | chr2:178633557;178633556;178633555 | chr2:179498284;179498283;179498282 |
| N2AB | 12627 | 38104;38105;38106 | chr2:178633557;178633556;178633555 | chr2:179498284;179498283;179498282 |
| N2A | 11700 | 35323;35324;35325 | chr2:178633557;178633556;178633555 | chr2:179498284;179498283;179498282 |
| N2B | 5203 | 15832;15833;15834 | chr2:178633557;178633556;178633555 | chr2:179498284;179498283;179498282 |
| Novex-1 | 5328 | 16207;16208;16209 | chr2:178633557;178633556;178633555 | chr2:179498284;179498283;179498282 |
| Novex-2 | 5395 | 16408;16409;16410 | chr2:178633557;178633556;178633555 | chr2:179498284;179498283;179498282 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | None | None | 0.999 | D | 0.678 | 0.456 | 0.612639375224 | gnomAD-4.0.0 | 6.8438E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9959E-07 | 0 | 0 |
| E/Q | None | None | 1.0 | D | 0.618 | 0.388 | 0.460526725402 | gnomAD-4.0.0 | 2.05315E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69877E-06 | 0 | 0 |
| E/V | None | None | 1.0 | D | 0.691 | 0.489 | 0.737197789486 | gnomAD-4.0.0 | 6.8438E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15939E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1836 | likely_benign | 0.1465 | benign | -0.52 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | D | 0.563067458 | None | None | N |
| E/C | 0.9302 | likely_pathogenic | 0.9004 | pathogenic | -0.434 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/D | 0.2728 | likely_benign | 0.2229 | benign | -0.618 | Destabilizing | 0.999 | D | 0.51 | neutral | D | 0.583622178 | None | None | N |
| E/F | 0.8858 | likely_pathogenic | 0.8118 | pathogenic | 0.133 | Stabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| E/G | 0.3628 | ambiguous | 0.2361 | benign | -0.819 | Destabilizing | 1.0 | D | 0.65 | neutral | D | 0.683933654 | None | None | N |
| E/H | 0.7622 | likely_pathogenic | 0.6836 | pathogenic | 0.388 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| E/I | 0.3675 | ambiguous | 0.2909 | benign | 0.276 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| E/K | 0.2898 | likely_benign | 0.1982 | benign | -0.013 | Destabilizing | 0.999 | D | 0.651 | neutral | D | 0.56916916 | None | None | N |
| E/L | 0.4566 | ambiguous | 0.3829 | ambiguous | 0.276 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| E/M | 0.4874 | ambiguous | 0.3997 | ambiguous | 0.276 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| E/N | 0.3808 | ambiguous | 0.288 | benign | -0.703 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| E/P | 0.4404 | ambiguous | 0.4365 | ambiguous | 0.031 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| E/Q | 0.25 | likely_benign | 0.204 | benign | -0.574 | Destabilizing | 1.0 | D | 0.618 | neutral | D | 0.564542129 | None | None | N |
| E/R | 0.5508 | ambiguous | 0.4262 | ambiguous | 0.421 | Stabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| E/S | 0.3565 | ambiguous | 0.2743 | benign | -0.879 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| E/T | 0.288 | likely_benign | 0.2332 | benign | -0.618 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| E/V | 0.2244 | likely_benign | 0.1815 | benign | 0.031 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.559805697 | None | None | N |
| E/W | 0.9795 | likely_pathogenic | 0.9558 | pathogenic | 0.427 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| E/Y | 0.8431 | likely_pathogenic | 0.7349 | pathogenic | 0.409 | Stabilizing | 1.0 | D | 0.663 | 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.