Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29469 | 88630;88631;88632 | chr2:178555054;178555053;178555052 | chr2:179419781;179419780;179419779 |
| N2AB | 27828 | 83707;83708;83709 | chr2:178555054;178555053;178555052 | chr2:179419781;179419780;179419779 |
| N2A | 26901 | 80926;80927;80928 | chr2:178555054;178555053;178555052 | chr2:179419781;179419780;179419779 |
| N2B | 20404 | 61435;61436;61437 | chr2:178555054;178555053;178555052 | chr2:179419781;179419780;179419779 |
| Novex-1 | 20529 | 61810;61811;61812 | chr2:178555054;178555053;178555052 | chr2:179419781;179419780;179419779 |
| Novex-2 | 20596 | 62011;62012;62013 | chr2:178555054;178555053;178555052 | chr2:179419781;179419780;179419779 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.295 | N | 0.447 | 0.114 | 0.190952846119 | gnomAD-4.0.0 | 1.59132E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85798E-06 | 0 | 0 |
| A/T | rs1482444171  |
-0.532 | 0.055 | N | 0.283 | 0.09 | 0.163833314356 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 8.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs1482444171 |
-0.532 | 0.055 | N | 0.283 | 0.09 | 0.163833314356 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 3.27482E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs1482444171 |
-0.532 | 0.055 | N | 0.283 | 0.09 | 0.163833314356 | gnomAD-4.0.0 | 1.02491E-05 | None | None | None | None | I | None | 0 | 1.35584E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs397517740 |
-0.178 | 0.064 | N | 0.288 | 0.034 | 0.0986583533028 | gnomAD-2.1.1 | 8.94E-05 | None | None | None | None | I | None | 0 | 1.13193E-04 | None | 0 | 6.1792E-04 | None | 2.61523E-04 | None | 0 | 7.83E-06 | 0 |
| A/V | rs397517740 |
-0.178 | 0.064 | N | 0.288 | 0.034 | 0.0986583533028 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 3.85356E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs397517740 |
-0.178 | 0.064 | N | 0.288 | 0.034 | 0.0986583533028 | gnomAD-4.0.0 | 5.32967E-05 | None | None | None | None | I | None | 2.67058E-05 | 5.0015E-05 | None | 0 | 9.81924E-04 | None | 0 | 0 | 8.47583E-06 | 2.85482E-04 | 1.60118E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4076 | ambiguous | 0.3962 | ambiguous | -0.695 | Destabilizing | 0.864 | D | 0.421 | neutral | None | None | None | None | I |
| A/D | 0.1815 | likely_benign | 0.132 | benign | -0.67 | Destabilizing | None | N | 0.253 | neutral | None | None | None | None | I |
| A/E | 0.11 | likely_benign | 0.0855 | benign | -0.835 | Destabilizing | None | N | 0.177 | neutral | N | 0.465562329 | None | None | I |
| A/F | 0.2517 | likely_benign | 0.2238 | benign | -0.957 | Destabilizing | 0.001 | N | 0.323 | neutral | None | None | None | None | I |
| A/G | 0.1642 | likely_benign | 0.1561 | benign | -0.286 | Destabilizing | 0.13 | N | 0.268 | neutral | D | 0.530115239 | None | None | I |
| A/H | 0.3383 | likely_benign | 0.296 | benign | -0.385 | Destabilizing | 0.356 | N | 0.547 | neutral | None | None | None | None | I |
| A/I | 0.1183 | likely_benign | 0.1065 | benign | -0.378 | Destabilizing | None | N | 0.251 | neutral | None | None | None | None | I |
| A/K | 0.2364 | likely_benign | 0.1894 | benign | -0.687 | Destabilizing | 0.038 | N | 0.416 | neutral | None | None | None | None | I |
| A/L | 0.0963 | likely_benign | 0.087 | benign | -0.378 | Destabilizing | 0.016 | N | 0.381 | neutral | None | None | None | None | I |
| A/M | 0.1309 | likely_benign | 0.1212 | benign | -0.413 | Destabilizing | 0.214 | N | 0.455 | neutral | None | None | None | None | I |
| A/N | 0.189 | likely_benign | 0.1578 | benign | -0.296 | Destabilizing | 0.038 | N | 0.521 | neutral | None | None | None | None | I |
| A/P | 0.109 | likely_benign | 0.1063 | benign | -0.307 | Destabilizing | 0.295 | N | 0.447 | neutral | N | 0.411903989 | None | None | I |
| A/Q | 0.1687 | likely_benign | 0.1426 | benign | -0.605 | Destabilizing | 0.007 | N | 0.246 | neutral | None | None | None | None | I |
| A/R | 0.2528 | likely_benign | 0.2089 | benign | -0.198 | Destabilizing | 0.12 | N | 0.442 | neutral | None | None | None | None | I |
| A/S | 0.0926 | likely_benign | 0.0913 | benign | -0.437 | Destabilizing | 0.012 | N | 0.316 | neutral | N | 0.499445616 | None | None | I |
| A/T | 0.0715 | likely_benign | 0.0722 | benign | -0.534 | Destabilizing | 0.055 | N | 0.283 | neutral | N | 0.456462843 | None | None | I |
| A/V | 0.0759 | likely_benign | 0.0711 | benign | -0.307 | Destabilizing | 0.064 | N | 0.288 | neutral | N | 0.48380416 | None | None | I |
| A/W | 0.5925 | likely_pathogenic | 0.5437 | ambiguous | -1.093 | Destabilizing | 0.864 | D | 0.587 | neutral | None | None | None | None | I |
| A/Y | 0.3419 | ambiguous | 0.2841 | benign | -0.755 | Destabilizing | 0.12 | N | 0.545 | 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.