Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26119 | 78580;78581;78582 | chr2:178567777;178567776;178567775 | chr2:179432504;179432503;179432502 |
| N2AB | 24478 | 73657;73658;73659 | chr2:178567777;178567776;178567775 | chr2:179432504;179432503;179432502 |
| N2A | 23551 | 70876;70877;70878 | chr2:178567777;178567776;178567775 | chr2:179432504;179432503;179432502 |
| N2B | 17054 | 51385;51386;51387 | chr2:178567777;178567776;178567775 | chr2:179432504;179432503;179432502 |
| Novex-1 | 17179 | 51760;51761;51762 | chr2:178567777;178567776;178567775 | chr2:179432504;179432503;179432502 |
| Novex-2 | 17246 | 51961;51962;51963 | chr2:178567777;178567776;178567775 | chr2:179432504;179432503;179432502 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | None | None | 0.007 | N | 0.347 | 0.075 | 0.30212335484 | gnomAD-4.0.0 | 2.73737E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47899E-05 | 1.657E-05 |
| M/V | rs1231026101  |
0.379 | None | N | 0.091 | 0.07 | 0.233785782151 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| M/V | rs1231026101 |
0.379 | None | N | 0.091 | 0.07 | 0.233785782151 | gnomAD-4.0.0 | 4.79036E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39763E-06 | 0 | 1.657E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2514 | likely_benign | 0.2005 | benign | -0.351 | Destabilizing | 0.002 | N | 0.215 | neutral | None | None | None | None | I |
| M/C | 0.6498 | likely_pathogenic | 0.5642 | pathogenic | -0.288 | Destabilizing | 0.245 | N | 0.398 | neutral | None | None | None | None | I |
| M/D | 0.7828 | likely_pathogenic | 0.7047 | pathogenic | 0.483 | Stabilizing | 0.044 | N | 0.511 | neutral | None | None | None | None | I |
| M/E | 0.4506 | ambiguous | 0.3921 | ambiguous | 0.42 | Stabilizing | 0.009 | N | 0.364 | neutral | None | None | None | None | I |
| M/F | 0.4447 | ambiguous | 0.3471 | ambiguous | -0.162 | Destabilizing | 0.044 | N | 0.283 | neutral | None | None | None | None | I |
| M/G | 0.5321 | ambiguous | 0.4232 | ambiguous | -0.507 | Destabilizing | 0.018 | N | 0.424 | neutral | None | None | None | None | I |
| M/H | 0.4032 | ambiguous | 0.3362 | benign | 0.238 | Stabilizing | 0.245 | N | 0.44 | neutral | None | None | None | None | I |
| M/I | 0.2638 | likely_benign | 0.1838 | benign | -0.045 | Destabilizing | 0.001 | N | 0.167 | neutral | N | 0.412281551 | None | None | I |
| M/K | 0.079 | likely_benign | 0.0844 | benign | 0.654 | Stabilizing | None | N | 0.131 | neutral | N | 0.293664869 | None | None | I |
| M/L | 0.1084 | likely_benign | 0.093 | benign | -0.045 | Destabilizing | None | N | 0.071 | neutral | N | 0.396216021 | None | None | I |
| M/N | 0.417 | ambiguous | 0.3236 | benign | 0.786 | Stabilizing | 0.044 | N | 0.5 | neutral | None | None | None | None | I |
| M/P | 0.465 | ambiguous | 0.3502 | ambiguous | -0.118 | Destabilizing | 0.085 | N | 0.52 | neutral | None | None | None | None | I |
| M/Q | 0.1578 | likely_benign | 0.1491 | benign | 0.601 | Stabilizing | 0.022 | N | 0.281 | neutral | None | None | None | None | I |
| M/R | 0.129 | likely_benign | 0.121 | benign | 1.097 | Stabilizing | 0.007 | N | 0.369 | neutral | N | 0.332876618 | None | None | I |
| M/S | 0.3399 | likely_benign | 0.2607 | benign | 0.32 | Stabilizing | 0.009 | N | 0.365 | neutral | None | None | None | None | I |
| M/T | 0.1783 | likely_benign | 0.1472 | benign | 0.36 | Stabilizing | 0.007 | N | 0.347 | neutral | N | 0.372723086 | None | None | I |
| M/V | 0.0667 | likely_benign | 0.0541 | benign | -0.118 | Destabilizing | None | N | 0.091 | neutral | N | 0.392175638 | None | None | I |
| M/W | 0.7378 | likely_pathogenic | 0.6414 | pathogenic | -0.14 | Destabilizing | 0.788 | D | 0.396 | neutral | None | None | None | None | I |
| M/Y | 0.5921 | likely_pathogenic | 0.4967 | ambiguous | 0.059 | Stabilizing | 0.085 | N | 0.446 | 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.