Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1749 | 5470;5471;5472 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
| N2AB | 1749 | 5470;5471;5472 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
| N2A | 1749 | 5470;5471;5472 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
| N2B | 1703 | 5332;5333;5334 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
| Novex-1 | 1703 | 5332;5333;5334 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
| Novex-2 | 1703 | 5332;5333;5334 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
| Novex-3 | 1749 | 5470;5471;5472 | chr2:178776619;178776618;178776617 | chr2:179641346;179641345;179641344 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | None | None | 1.0 | N | 0.621 | 0.353 | 0.251639045875 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| N/S | rs1304904777  |
None | 0.999 | N | 0.504 | 0.407 | 0.252162846088 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs1304904777 |
None | 0.999 | N | 0.504 | 0.407 | 0.252162846088 | gnomAD-4.0.0 | 6.56883E-06 | None | None | None | None | I | None | 0 | 0 | None | 2.88351E-04 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.7068 | likely_pathogenic | 0.5569 | ambiguous | -0.076 | Destabilizing | 1.0 | D | 0.534 | neutral | None | None | None | None | I |
| N/C | 0.8465 | likely_pathogenic | 0.7832 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| N/D | 0.6094 | likely_pathogenic | 0.4849 | ambiguous | -0.1 | Destabilizing | 0.999 | D | 0.559 | neutral | N | 0.504577533 | None | None | I |
| N/E | 0.8895 | likely_pathogenic | 0.8173 | pathogenic | -0.17 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | I |
| N/F | 0.9507 | likely_pathogenic | 0.9034 | pathogenic | -0.742 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| N/G | 0.581 | likely_pathogenic | 0.4692 | ambiguous | -0.13 | Destabilizing | 0.999 | D | 0.501 | neutral | None | None | None | None | I |
| N/H | 0.4667 | ambiguous | 0.3506 | ambiguous | -0.144 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | N | 0.502028615 | None | None | I |
| N/I | 0.8492 | likely_pathogenic | 0.7156 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | D | 0.613289852 | None | None | I |
| N/K | 0.9013 | likely_pathogenic | 0.8144 | pathogenic | -0.047 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.503496206 | None | None | I |
| N/L | 0.7358 | likely_pathogenic | 0.6209 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| N/M | 0.875 | likely_pathogenic | 0.7822 | pathogenic | -0.067 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| N/P | 0.7818 | likely_pathogenic | 0.6368 | pathogenic | -0.025 | Destabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | I |
| N/Q | 0.8116 | likely_pathogenic | 0.7062 | pathogenic | -0.334 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| N/R | 0.871 | likely_pathogenic | 0.7813 | pathogenic | 0.037 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| N/S | 0.1588 | likely_benign | 0.1247 | benign | -0.125 | Destabilizing | 0.999 | D | 0.504 | neutral | N | 0.4525387 | None | None | I |
| N/T | 0.4797 | ambiguous | 0.3538 | ambiguous | -0.105 | Destabilizing | 0.999 | D | 0.591 | neutral | N | 0.510168819 | None | None | I |
| N/V | 0.7771 | likely_pathogenic | 0.6425 | pathogenic | -0.025 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| N/W | 0.9825 | likely_pathogenic | 0.9612 | pathogenic | -0.931 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| N/Y | 0.7206 | likely_pathogenic | 0.584 | pathogenic | -0.598 | Destabilizing | 1.0 | D | 0.637 | neutral | D | 0.58353678 | 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.