Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18911 | 56956;56957;56958 | chr2:178598979;178598978;178598977 | chr2:179463706;179463705;179463704 |
| N2AB | 17270 | 52033;52034;52035 | chr2:178598979;178598978;178598977 | chr2:179463706;179463705;179463704 |
| N2A | 16343 | 49252;49253;49254 | chr2:178598979;178598978;178598977 | chr2:179463706;179463705;179463704 |
| N2B | 9846 | 29761;29762;29763 | chr2:178598979;178598978;178598977 | chr2:179463706;179463705;179463704 |
| Novex-1 | 9971 | 30136;30137;30138 | chr2:178598979;178598978;178598977 | chr2:179463706;179463705;179463704 |
| Novex-2 | 10038 | 30337;30338;30339 | chr2:178598979;178598978;178598977 | chr2:179463706;179463705;179463704 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1225577870  |
-0.596 | 1.0 | N | 0.465 | 0.302 | 0.358340041657 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| D/E | rs1225577870 |
-0.596 | 1.0 | N | 0.465 | 0.302 | 0.358340041657 | gnomAD-4.0.0 | 6.84891E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16098E-05 | 0 |
| D/G | rs1296392570 |
-1.15 | 1.0 | N | 0.728 | 0.513 | 0.420447328233 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.07E-06 | 0 |
| D/G | rs1296392570 |
-1.15 | 1.0 | N | 0.728 | 0.513 | 0.420447328233 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs1296392570 |
-1.15 | 1.0 | N | 0.728 | 0.513 | 0.420447328233 | gnomAD-4.0.0 | 4.34222E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93618E-06 | 0 | 0 |
| D/H | None | None | 1.0 | N | 0.707 | 0.447 | 0.430694319191 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9254 | likely_pathogenic | 0.9224 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.486145358 | None | None | I |
| D/C | 0.9847 | likely_pathogenic | 0.9816 | pathogenic | -0.298 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| D/E | 0.9257 | likely_pathogenic | 0.9322 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.465 | neutral | N | 0.483650143 | None | None | I |
| D/F | 0.9919 | likely_pathogenic | 0.9915 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| D/G | 0.8858 | likely_pathogenic | 0.8869 | pathogenic | -1.069 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.508239312 | None | None | I |
| D/H | 0.9467 | likely_pathogenic | 0.943 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.497603795 | None | None | I |
| D/I | 0.9846 | likely_pathogenic | 0.9836 | pathogenic | 0.075 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| D/K | 0.9807 | likely_pathogenic | 0.981 | pathogenic | -0.42 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| D/L | 0.9725 | likely_pathogenic | 0.9719 | pathogenic | 0.075 | Stabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | I |
| D/M | 0.9919 | likely_pathogenic | 0.9922 | pathogenic | 0.557 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/N | 0.2954 | likely_benign | 0.3126 | benign | -0.789 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.502840133 | None | None | I |
| D/P | 0.9868 | likely_pathogenic | 0.9873 | pathogenic | -0.178 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| D/Q | 0.9746 | likely_pathogenic | 0.9751 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | I |
| D/R | 0.9774 | likely_pathogenic | 0.9772 | pathogenic | -0.316 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| D/S | 0.6248 | likely_pathogenic | 0.6222 | pathogenic | -1.027 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| D/T | 0.7661 | likely_pathogenic | 0.8027 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| D/V | 0.9519 | likely_pathogenic | 0.9495 | pathogenic | -0.178 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.504503103 | None | None | I |
| D/W | 0.998 | likely_pathogenic | 0.9979 | pathogenic | -0.332 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| D/Y | 0.9417 | likely_pathogenic | 0.9293 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.519760202 | 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.