Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28048 | 84367;84368;84369 | chr2:178561990;178561989;178561988 | chr2:179426717;179426716;179426715 |
| N2AB | 26407 | 79444;79445;79446 | chr2:178561990;178561989;178561988 | chr2:179426717;179426716;179426715 |
| N2A | 25480 | 76663;76664;76665 | chr2:178561990;178561989;178561988 | chr2:179426717;179426716;179426715 |
| N2B | 18983 | 57172;57173;57174 | chr2:178561990;178561989;178561988 | chr2:179426717;179426716;179426715 |
| Novex-1 | 19108 | 57547;57548;57549 | chr2:178561990;178561989;178561988 | chr2:179426717;179426716;179426715 |
| Novex-2 | 19175 | 57748;57749;57750 | chr2:178561990;178561989;178561988 | chr2:179426717;179426716;179426715 |
| 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/T | rs770523023  |
-2.194 | 0.549 | N | 0.676 | 0.447 | 0.709290299383 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs770523023 |
-2.194 | 0.549 | N | 0.676 | 0.447 | 0.709290299383 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs770523023 |
-2.194 | 0.549 | N | 0.676 | 0.447 | 0.709290299383 | gnomAD-4.0.0 | 3.04483E-06 | None | None | None | None | I | None | 3.49369E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20491E-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 | 0.7597 | likely_pathogenic | 0.7916 | pathogenic | -2.124 | Highly Destabilizing | 0.4 | N | 0.62 | neutral | None | None | None | None | I |
| I/C | 0.8262 | likely_pathogenic | 0.8245 | pathogenic | -1.363 | Destabilizing | 0.992 | D | 0.695 | prob.neutral | None | None | None | None | I |
| I/D | 0.9932 | likely_pathogenic | 0.9957 | pathogenic | -2.792 | Highly Destabilizing | 0.972 | D | 0.779 | deleterious | None | None | None | None | I |
| I/E | 0.9826 | likely_pathogenic | 0.9882 | pathogenic | -2.457 | Highly Destabilizing | 0.92 | D | 0.773 | deleterious | None | None | None | None | I |
| I/F | 0.2472 | likely_benign | 0.2667 | benign | -1.269 | Destabilizing | 0.681 | D | 0.675 | prob.neutral | N | 0.484669279 | None | None | I |
| I/G | 0.9636 | likely_pathogenic | 0.9694 | pathogenic | -2.74 | Highly Destabilizing | 0.92 | D | 0.779 | deleterious | None | None | None | None | I |
| I/H | 0.9605 | likely_pathogenic | 0.9718 | pathogenic | -2.717 | Highly Destabilizing | 0.992 | D | 0.747 | deleterious | None | None | None | None | I |
| I/K | 0.9629 | likely_pathogenic | 0.9751 | pathogenic | -1.482 | Destabilizing | 0.85 | D | 0.779 | deleterious | None | None | None | None | I |
| I/L | 0.0831 | likely_benign | 0.0961 | benign | -0.274 | Destabilizing | 0.002 | N | 0.168 | neutral | N | 0.490343343 | None | None | I |
| I/M | 0.1258 | likely_benign | 0.1433 | benign | -0.536 | Destabilizing | 0.099 | N | 0.484 | neutral | D | 0.527981361 | None | None | I |
| I/N | 0.9269 | likely_pathogenic | 0.9508 | pathogenic | -2.233 | Highly Destabilizing | 0.896 | D | 0.775 | deleterious | D | 0.52848834 | None | None | I |
| I/P | 0.9883 | likely_pathogenic | 0.9912 | pathogenic | -0.882 | Destabilizing | 0.972 | D | 0.78 | deleterious | None | None | None | None | I |
| I/Q | 0.957 | likely_pathogenic | 0.9686 | pathogenic | -1.786 | Destabilizing | 0.92 | D | 0.771 | deleterious | None | None | None | None | I |
| I/R | 0.944 | likely_pathogenic | 0.9614 | pathogenic | -1.86 | Destabilizing | 0.92 | D | 0.779 | deleterious | None | None | None | None | I |
| I/S | 0.903 | likely_pathogenic | 0.9239 | pathogenic | -2.747 | Highly Destabilizing | 0.81 | D | 0.74 | deleterious | N | 0.498013821 | None | None | I |
| I/T | 0.8338 | likely_pathogenic | 0.8573 | pathogenic | -2.23 | Highly Destabilizing | 0.549 | D | 0.676 | prob.neutral | N | 0.504090208 | None | None | I |
| I/V | 0.0811 | likely_benign | 0.0774 | benign | -0.882 | Destabilizing | 0.016 | N | 0.167 | neutral | N | 0.491055419 | None | None | I |
| I/W | 0.9534 | likely_pathogenic | 0.9606 | pathogenic | -1.657 | Destabilizing | 0.992 | D | 0.756 | deleterious | None | None | None | None | I |
| I/Y | 0.8431 | likely_pathogenic | 0.8625 | pathogenic | -1.391 | Destabilizing | 0.92 | D | 0.745 | 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.