Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18109 | 54550;54551;54552 | chr2:178604764;178604763;178604762 | chr2:179469491;179469490;179469489 |
| N2AB | 16468 | 49627;49628;49629 | chr2:178604764;178604763;178604762 | chr2:179469491;179469490;179469489 |
| N2A | 15541 | 46846;46847;46848 | chr2:178604764;178604763;178604762 | chr2:179469491;179469490;179469489 |
| N2B | 9044 | 27355;27356;27357 | chr2:178604764;178604763;178604762 | chr2:179469491;179469490;179469489 |
| Novex-1 | 9169 | 27730;27731;27732 | chr2:178604764;178604763;178604762 | chr2:179469491;179469490;179469489 |
| Novex-2 | 9236 | 27931;27932;27933 | chr2:178604764;178604763;178604762 | chr2:179469491;179469490;179469489 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.005 | N | 0.163 | 0.211 | 0.350746614512 | gnomAD-4.0.0 | 6.8482E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16163E-05 | 0 |
| R/K | rs1422300331  |
0.082 | 0.005 | N | 0.14 | 0.084 | 0.162503812791 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/K | rs1422300331 |
0.082 | 0.005 | N | 0.14 | 0.084 | 0.162503812791 | gnomAD-4.0.0 | 1.59496E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03141E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5846 | likely_pathogenic | 0.5195 | ambiguous | -0.18 | Destabilizing | 0.688 | D | 0.311 | neutral | None | None | None | None | N |
| R/C | 0.3331 | likely_benign | 0.2916 | benign | -0.206 | Destabilizing | 0.998 | D | 0.328 | neutral | None | None | None | None | N |
| R/D | 0.8075 | likely_pathogenic | 0.7814 | pathogenic | -0.152 | Destabilizing | 0.842 | D | 0.319 | neutral | None | None | None | None | N |
| R/E | 0.5552 | ambiguous | 0.5037 | ambiguous | -0.113 | Destabilizing | 0.728 | D | 0.238 | neutral | None | None | None | None | N |
| R/F | 0.7529 | likely_pathogenic | 0.7191 | pathogenic | -0.492 | Destabilizing | 0.991 | D | 0.292 | neutral | None | None | None | None | N |
| R/G | 0.3777 | ambiguous | 0.3287 | benign | -0.342 | Destabilizing | 0.005 | N | 0.163 | neutral | N | 0.426760719 | None | None | N |
| R/H | 0.1857 | likely_benign | 0.1718 | benign | -0.779 | Destabilizing | 0.991 | D | 0.245 | neutral | None | None | None | None | N |
| R/I | 0.4841 | ambiguous | 0.451 | ambiguous | 0.207 | Stabilizing | 0.974 | D | 0.311 | neutral | None | None | None | None | N |
| R/K | 0.1095 | likely_benign | 0.1123 | benign | -0.181 | Destabilizing | 0.005 | N | 0.14 | neutral | N | 0.351937674 | None | None | N |
| R/L | 0.4007 | ambiguous | 0.3586 | ambiguous | 0.207 | Stabilizing | 0.842 | D | 0.307 | neutral | None | None | None | None | N |
| R/M | 0.5044 | ambiguous | 0.4573 | ambiguous | -0.007 | Destabilizing | 0.989 | D | 0.283 | neutral | N | 0.443079753 | None | None | N |
| R/N | 0.7216 | likely_pathogenic | 0.7056 | pathogenic | 0.142 | Stabilizing | 0.842 | D | 0.253 | neutral | None | None | None | None | N |
| R/P | 0.8097 | likely_pathogenic | 0.7658 | pathogenic | 0.097 | Stabilizing | 0.974 | D | 0.318 | neutral | None | None | None | None | N |
| R/Q | 0.1511 | likely_benign | 0.1355 | benign | -0.045 | Destabilizing | 0.842 | D | 0.261 | neutral | None | None | None | None | N |
| R/S | 0.6789 | likely_pathogenic | 0.6347 | pathogenic | -0.259 | Destabilizing | 0.801 | D | 0.285 | neutral | N | 0.410503188 | None | None | N |
| R/T | 0.4919 | ambiguous | 0.4277 | ambiguous | -0.104 | Destabilizing | 0.801 | D | 0.319 | neutral | N | 0.412986132 | None | None | N |
| R/V | 0.5265 | ambiguous | 0.4737 | ambiguous | 0.097 | Stabilizing | 0.974 | D | 0.333 | neutral | None | None | None | None | N |
| R/W | 0.3535 | ambiguous | 0.3076 | benign | -0.526 | Destabilizing | 0.997 | D | 0.354 | neutral | N | 0.464532461 | None | None | N |
| R/Y | 0.6047 | likely_pathogenic | 0.5865 | pathogenic | -0.126 | Destabilizing | 0.991 | D | 0.282 | 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.