Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16793 | 50602;50603;50604 | chr2:178611932;178611931;178611930 | chr2:179476659;179476658;179476657 |
| N2AB | 15152 | 45679;45680;45681 | chr2:178611932;178611931;178611930 | chr2:179476659;179476658;179476657 |
| N2A | 14225 | 42898;42899;42900 | chr2:178611932;178611931;178611930 | chr2:179476659;179476658;179476657 |
| N2B | 7728 | 23407;23408;23409 | chr2:178611932;178611931;178611930 | chr2:179476659;179476658;179476657 |
| Novex-1 | 7853 | 23782;23783;23784 | chr2:178611932;178611931;178611930 | chr2:179476659;179476658;179476657 |
| Novex-2 | 7920 | 23983;23984;23985 | chr2:178611932;178611931;178611930 | chr2:179476659;179476658;179476657 |
| 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/K | rs1446626288  |
-0.266 | None | N | 0.171 | 0.139 | 0.144782658237 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| R/K | rs1446626288 |
-0.266 | None | N | 0.171 | 0.139 | 0.144782658237 | gnomAD-4.0.0 | 1.59566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86346E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4796 | ambiguous | 0.4911 | ambiguous | 0.085 | Stabilizing | 0.007 | N | 0.339 | neutral | None | None | None | None | N |
| R/C | 0.4104 | ambiguous | 0.3979 | ambiguous | -0.13 | Destabilizing | 0.864 | D | 0.451 | neutral | None | None | None | None | N |
| R/D | 0.839 | likely_pathogenic | 0.8499 | pathogenic | -0.107 | Destabilizing | 0.031 | N | 0.485 | neutral | None | None | None | None | N |
| R/E | 0.5511 | ambiguous | 0.5364 | ambiguous | -0.032 | Destabilizing | 0.007 | N | 0.189 | neutral | None | None | None | None | N |
| R/F | 0.7524 | likely_pathogenic | 0.7611 | pathogenic | -0.128 | Destabilizing | 0.628 | D | 0.472 | neutral | None | None | None | None | N |
| R/G | 0.3809 | ambiguous | 0.3944 | ambiguous | -0.116 | Destabilizing | 0.024 | N | 0.491 | neutral | N | 0.447316098 | None | None | N |
| R/H | 0.2454 | likely_benign | 0.2449 | benign | -0.703 | Destabilizing | 0.356 | N | 0.357 | neutral | None | None | None | None | N |
| R/I | 0.3841 | ambiguous | 0.3917 | ambiguous | 0.577 | Stabilizing | 0.136 | N | 0.485 | neutral | None | None | None | None | N |
| R/K | 0.0589 | likely_benign | 0.054 | benign | -0.002 | Destabilizing | None | N | 0.171 | neutral | N | 0.30192853 | None | None | N |
| R/L | 0.3392 | likely_benign | 0.34 | benign | 0.577 | Stabilizing | 0.031 | N | 0.491 | neutral | None | None | None | None | N |
| R/M | 0.3449 | ambiguous | 0.3621 | ambiguous | 0.044 | Stabilizing | 0.56 | D | 0.435 | neutral | N | 0.470102332 | None | None | N |
| R/N | 0.6409 | likely_pathogenic | 0.6713 | pathogenic | 0.139 | Stabilizing | 0.031 | N | 0.291 | neutral | None | None | None | None | N |
| R/P | 0.6743 | likely_pathogenic | 0.7244 | pathogenic | 0.434 | Stabilizing | 0.136 | N | 0.504 | neutral | None | None | None | None | N |
| R/Q | 0.1634 | likely_benign | 0.1592 | benign | 0.098 | Stabilizing | 0.016 | N | 0.313 | neutral | None | None | None | None | N |
| R/S | 0.6225 | likely_pathogenic | 0.6311 | pathogenic | -0.144 | Destabilizing | 0.012 | N | 0.399 | neutral | N | 0.413998421 | None | None | N |
| R/T | 0.3891 | ambiguous | 0.4109 | ambiguous | 0.071 | Stabilizing | 0.024 | N | 0.457 | neutral | N | 0.395954944 | None | None | N |
| R/V | 0.4627 | ambiguous | 0.4609 | ambiguous | 0.434 | Stabilizing | 0.072 | N | 0.503 | neutral | None | None | None | None | N |
| R/W | 0.4343 | ambiguous | 0.4606 | ambiguous | -0.23 | Destabilizing | 0.828 | D | 0.461 | neutral | N | 0.482584236 | None | None | N |
| R/Y | 0.6298 | likely_pathogenic | 0.6262 | pathogenic | 0.193 | Stabilizing | 0.356 | N | 0.471 | 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.