Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22186 | 66781;66782;66783 | chr2:178581712;178581711;178581710 | chr2:179446439;179446438;179446437 |
| N2AB | 20545 | 61858;61859;61860 | chr2:178581712;178581711;178581710 | chr2:179446439;179446438;179446437 |
| N2A | 19618 | 59077;59078;59079 | chr2:178581712;178581711;178581710 | chr2:179446439;179446438;179446437 |
| N2B | 13121 | 39586;39587;39588 | chr2:178581712;178581711;178581710 | chr2:179446439;179446438;179446437 |
| Novex-1 | 13246 | 39961;39962;39963 | chr2:178581712;178581711;178581710 | chr2:179446439;179446438;179446437 |
| Novex-2 | 13313 | 40162;40163;40164 | chr2:178581712;178581711;178581710 | chr2:179446439;179446438;179446437 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.309 | N | 0.624 | 0.116 | 0.21279746466 | gnomAD-4.0.0 | 1.59774E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86761E-06 | 0 | 0 |
| S/N | rs529719640  |
-0.834 | 0.815 | N | 0.707 | 0.275 | 0.302459207581 | gnomAD-2.1.1 | 4.11E-06 | None | None | None | None | I | None | 6.65E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs529719640 |
-0.834 | 0.815 | N | 0.707 | 0.275 | 0.302459207581 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs529719640 |
-0.834 | 0.815 | N | 0.707 | 0.275 | 0.302459207581 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/N | rs529719640 |
-0.834 | 0.815 | N | 0.707 | 0.275 | 0.302459207581 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | I | None | 2.40639E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs750211489 |
-0.688 | 0.939 | N | 0.717 | 0.358 | 0.32471235697 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 0 | 0 |
| S/R | rs750211489 |
-0.688 | 0.939 | N | 0.717 | 0.358 | 0.32471235697 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.13907E-04 | 0 |
| S/R | rs750211489 |
-0.688 | 0.939 | N | 0.717 | 0.358 | 0.32471235697 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| S/R | rs750211489 |
-0.688 | 0.939 | N | 0.717 | 0.358 | 0.32471235697 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1353 | likely_benign | 0.1283 | benign | -0.638 | Destabilizing | 0.004 | N | 0.343 | neutral | None | None | None | None | I |
| S/C | 0.0871 | likely_benign | 0.0902 | benign | -0.481 | Destabilizing | 0.007 | N | 0.462 | neutral | N | 0.509710177 | None | None | I |
| S/D | 0.8619 | likely_pathogenic | 0.8676 | pathogenic | -0.531 | Destabilizing | 0.854 | D | 0.713 | prob.delet. | None | None | None | None | I |
| S/E | 0.8707 | likely_pathogenic | 0.875 | pathogenic | -0.57 | Destabilizing | 0.742 | D | 0.708 | prob.delet. | None | None | None | None | I |
| S/F | 0.4165 | ambiguous | 0.4328 | ambiguous | -0.99 | Destabilizing | 0.953 | D | 0.741 | deleterious | None | None | None | None | I |
| S/G | 0.2563 | likely_benign | 0.2504 | benign | -0.84 | Destabilizing | 0.309 | N | 0.624 | neutral | N | 0.462095485 | None | None | I |
| S/H | 0.6536 | likely_pathogenic | 0.691 | pathogenic | -1.406 | Destabilizing | 0.996 | D | 0.677 | prob.neutral | None | None | None | None | I |
| S/I | 0.4539 | ambiguous | 0.4651 | ambiguous | -0.218 | Destabilizing | 0.884 | D | 0.741 | deleterious | N | 0.499085053 | None | None | I |
| S/K | 0.9626 | likely_pathogenic | 0.9699 | pathogenic | -0.786 | Destabilizing | 0.742 | D | 0.701 | prob.neutral | None | None | None | None | I |
| S/L | 0.1599 | likely_benign | 0.1593 | benign | -0.218 | Destabilizing | 0.59 | D | 0.665 | neutral | None | None | None | None | I |
| S/M | 0.3251 | likely_benign | 0.3125 | benign | 0.199 | Stabilizing | 0.984 | D | 0.687 | prob.neutral | None | None | None | None | I |
| S/N | 0.4384 | ambiguous | 0.4391 | ambiguous | -0.694 | Destabilizing | 0.815 | D | 0.707 | prob.neutral | N | 0.492501687 | None | None | I |
| S/P | 0.9895 | likely_pathogenic | 0.9911 | pathogenic | -0.326 | Destabilizing | 0.953 | D | 0.723 | prob.delet. | None | None | None | None | I |
| S/Q | 0.7916 | likely_pathogenic | 0.8093 | pathogenic | -0.951 | Destabilizing | 0.953 | D | 0.724 | prob.delet. | None | None | None | None | I |
| S/R | 0.9343 | likely_pathogenic | 0.9477 | pathogenic | -0.58 | Destabilizing | 0.939 | D | 0.717 | prob.delet. | N | 0.490473771 | None | None | I |
| S/T | 0.2203 | likely_benign | 0.209 | benign | -0.702 | Destabilizing | 0.472 | N | 0.618 | neutral | N | 0.47760021 | None | None | I |
| S/V | 0.4144 | ambiguous | 0.4221 | ambiguous | -0.326 | Destabilizing | 0.59 | D | 0.688 | prob.neutral | None | None | None | None | I |
| S/W | 0.6462 | likely_pathogenic | 0.7027 | pathogenic | -0.961 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | I |
| S/Y | 0.3944 | ambiguous | 0.4129 | ambiguous | -0.699 | Destabilizing | 0.984 | D | 0.733 | prob.delet. | 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.