Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21362 | 64309;64310;64311 | chr2:178587127;178587126;178587125 | chr2:179451854;179451853;179451852 |
| N2AB | 19721 | 59386;59387;59388 | chr2:178587127;178587126;178587125 | chr2:179451854;179451853;179451852 |
| N2A | 18794 | 56605;56606;56607 | chr2:178587127;178587126;178587125 | chr2:179451854;179451853;179451852 |
| N2B | 12297 | 37114;37115;37116 | chr2:178587127;178587126;178587125 | chr2:179451854;179451853;179451852 |
| Novex-1 | 12422 | 37489;37490;37491 | chr2:178587127;178587126;178587125 | chr2:179451854;179451853;179451852 |
| Novex-2 | 12489 | 37690;37691;37692 | chr2:178587127;178587126;178587125 | chr2:179451854;179451853;179451852 |
| 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/H | None | None | 1.0 | N | 0.801 | 0.322 | 0.229924730088 | gnomAD-4.0.0 | 1.59245E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88239E-05 | 0 | 0 | 0 | 0 |
| D/V | rs752967519  |
0.459 | 0.983 | N | 0.599 | 0.274 | 0.502752565406 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65893E-04 |
| D/Y | rs756650236 |
0.142 | 1.0 | N | 0.79 | 0.339 | 0.577502390439 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65837E-04 |
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 | 0.6508 | likely_pathogenic | 0.5548 | ambiguous | -0.263 | Destabilizing | 0.996 | D | 0.581 | neutral | N | 0.451328303 | None | None | N |
| D/C | 0.9338 | likely_pathogenic | 0.9082 | pathogenic | 0.108 | Stabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| D/E | 0.6165 | likely_pathogenic | 0.4925 | ambiguous | -0.32 | Destabilizing | 0.999 | D | 0.477 | neutral | N | 0.468375268 | None | None | N |
| D/F | 0.91 | likely_pathogenic | 0.858 | pathogenic | -0.367 | Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| D/G | 0.8476 | likely_pathogenic | 0.7481 | pathogenic | -0.412 | Destabilizing | 1.0 | D | 0.723 | deleterious | N | 0.503295919 | None | None | N |
| D/H | 0.7378 | likely_pathogenic | 0.6499 | pathogenic | -0.128 | Destabilizing | 1.0 | D | 0.801 | deleterious | N | 0.486326311 | None | None | N |
| D/I | 0.8937 | likely_pathogenic | 0.8136 | pathogenic | 0.07 | Stabilizing | 0.914 | D | 0.571 | neutral | None | None | None | None | N |
| D/K | 0.9317 | likely_pathogenic | 0.8861 | pathogenic | 0.383 | Stabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| D/L | 0.8409 | likely_pathogenic | 0.7646 | pathogenic | 0.07 | Stabilizing | 0.987 | D | 0.597 | neutral | None | None | None | None | N |
| D/M | 0.948 | likely_pathogenic | 0.9149 | pathogenic | 0.22 | Stabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| D/N | 0.36 | ambiguous | 0.2912 | benign | 0.159 | Stabilizing | 1.0 | D | 0.775 | deleterious | N | 0.463604167 | None | None | N |
| D/P | 0.9481 | likely_pathogenic | 0.8999 | pathogenic | -0.021 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/Q | 0.8757 | likely_pathogenic | 0.8102 | pathogenic | 0.165 | Stabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/R | 0.9335 | likely_pathogenic | 0.8924 | pathogenic | 0.485 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| D/S | 0.4603 | ambiguous | 0.3602 | ambiguous | 0.075 | Stabilizing | 1.0 | D | 0.737 | deleterious | None | None | None | None | N |
| D/T | 0.8058 | likely_pathogenic | 0.697 | pathogenic | 0.189 | Stabilizing | 0.999 | D | 0.746 | deleterious | None | None | None | None | N |
| D/V | 0.7729 | likely_pathogenic | 0.6597 | pathogenic | -0.021 | Destabilizing | 0.983 | D | 0.599 | neutral | N | 0.467322498 | None | None | N |
| D/W | 0.9826 | likely_pathogenic | 0.9755 | pathogenic | -0.286 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| D/Y | 0.6347 | likely_pathogenic | 0.5274 | ambiguous | -0.145 | Destabilizing | 1.0 | D | 0.79 | deleterious | N | 0.465462847 | 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.