Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33700 | 101323;101324;101325 | chr2:178535517;178535516;178535515 | chr2:179400244;179400243;179400242 |
| N2AB | 32059 | 96400;96401;96402 | chr2:178535517;178535516;178535515 | chr2:179400244;179400243;179400242 |
| N2A | 31132 | 93619;93620;93621 | chr2:178535517;178535516;178535515 | chr2:179400244;179400243;179400242 |
| N2B | 24635 | 74128;74129;74130 | chr2:178535517;178535516;178535515 | chr2:179400244;179400243;179400242 |
| Novex-1 | 24760 | 74503;74504;74505 | chr2:178535517;178535516;178535515 | chr2:179400244;179400243;179400242 |
| Novex-2 | 24827 | 74704;74705;74706 | chr2:178535517;178535516;178535515 | chr2:179400244;179400243;179400242 |
| 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/G | None | None | 0.557 | N | 0.569 | 0.334 | 0.283761946502 | gnomAD-4.0.0 | 1.36839E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79888E-06 | 0 | 0 |
| D/H | rs878858552  |
None | 0.984 | N | 0.586 | 0.404 | 0.333906830038 | gnomAD-4.0.0 | 2.73678E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59776E-06 | 0 | 0 |
| D/N | None | None | 0.436 | N | 0.539 | 0.233 | 0.208816687407 | gnomAD-4.0.0 | 6.84194E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65662E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4316 | ambiguous | 0.361 | ambiguous | -0.143 | Destabilizing | 0.634 | D | 0.511 | neutral | N | 0.518614875 | None | None | N |
| D/C | 0.8762 | likely_pathogenic | 0.8607 | pathogenic | 0.185 | Stabilizing | 0.982 | D | 0.647 | neutral | None | None | None | None | N |
| D/E | 0.2673 | likely_benign | 0.2842 | benign | -0.243 | Destabilizing | None | N | 0.183 | neutral | N | 0.443501041 | None | None | N |
| D/F | 0.9001 | likely_pathogenic | 0.8698 | pathogenic | -0.23 | Destabilizing | 0.994 | D | 0.649 | neutral | None | None | None | None | N |
| D/G | 0.454 | ambiguous | 0.3595 | ambiguous | -0.284 | Destabilizing | 0.557 | D | 0.569 | neutral | N | 0.472863268 | None | None | N |
| D/H | 0.668 | likely_pathogenic | 0.6205 | pathogenic | 0.059 | Stabilizing | 0.984 | D | 0.586 | neutral | N | 0.476043274 | None | None | N |
| D/I | 0.8209 | likely_pathogenic | 0.7871 | pathogenic | 0.166 | Stabilizing | 0.983 | D | 0.663 | neutral | None | None | None | None | N |
| D/K | 0.7617 | likely_pathogenic | 0.7158 | pathogenic | 0.614 | Stabilizing | 0.805 | D | 0.535 | neutral | None | None | None | None | N |
| D/L | 0.7835 | likely_pathogenic | 0.7434 | pathogenic | 0.166 | Stabilizing | 0.967 | D | 0.643 | neutral | None | None | None | None | N |
| D/M | 0.8941 | likely_pathogenic | 0.8819 | pathogenic | 0.254 | Stabilizing | 0.996 | D | 0.624 | neutral | None | None | None | None | N |
| D/N | 0.1897 | likely_benign | 0.1752 | benign | 0.319 | Stabilizing | 0.436 | N | 0.539 | neutral | N | 0.469783565 | None | None | N |
| D/P | 0.9769 | likely_pathogenic | 0.9544 | pathogenic | 0.083 | Stabilizing | 0.537 | D | 0.596 | neutral | None | None | None | None | N |
| D/Q | 0.679 | likely_pathogenic | 0.6535 | pathogenic | 0.329 | Stabilizing | 0.844 | D | 0.52 | neutral | None | None | None | None | N |
| D/R | 0.7911 | likely_pathogenic | 0.7281 | pathogenic | 0.684 | Stabilizing | 0.967 | D | 0.598 | neutral | None | None | None | None | N |
| D/S | 0.2944 | likely_benign | 0.2476 | benign | 0.258 | Stabilizing | 0.697 | D | 0.488 | neutral | None | None | None | None | N |
| D/T | 0.5659 | likely_pathogenic | 0.5324 | ambiguous | 0.373 | Stabilizing | 0.782 | D | 0.547 | neutral | None | None | None | None | N |
| D/V | 0.6172 | likely_pathogenic | 0.5477 | ambiguous | 0.083 | Stabilizing | 0.886 | D | 0.63 | neutral | N | 0.482017528 | None | None | N |
| D/W | 0.9791 | likely_pathogenic | 0.9746 | pathogenic | -0.151 | Destabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | N |
| D/Y | 0.6336 | likely_pathogenic | 0.5578 | ambiguous | 0.005 | Stabilizing | 0.993 | D | 0.651 | neutral | N | 0.496780875 | 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.