Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19106 | 57541;57542;57543 | chr2:178597766;178597765;178597764 | chr2:179462493;179462492;179462491 |
| N2AB | 17465 | 52618;52619;52620 | chr2:178597766;178597765;178597764 | chr2:179462493;179462492;179462491 |
| N2A | 16538 | 49837;49838;49839 | chr2:178597766;178597765;178597764 | chr2:179462493;179462492;179462491 |
| N2B | 10041 | 30346;30347;30348 | chr2:178597766;178597765;178597764 | chr2:179462493;179462492;179462491 |
| Novex-1 | 10166 | 30721;30722;30723 | chr2:178597766;178597765;178597764 | chr2:179462493;179462492;179462491 |
| Novex-2 | 10233 | 30922;30923;30924 | chr2:178597766;178597765;178597764 | chr2:179462493;179462492;179462491 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs754573037  |
-0.637 | 1.0 | N | 0.693 | 0.371 | 0.358948522604 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| A/T | rs754573037 |
-0.637 | 1.0 | N | 0.693 | 0.371 | 0.358948522604 | gnomAD-4.0.0 | 1.27402E-05 | None | None | None | None | I | None | 0 | 2.28948E-05 | None | 0 | 0 | None | 0 | 0 | 2.00189E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6216 | likely_pathogenic | 0.6765 | pathogenic | -0.618 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| A/D | 0.9072 | likely_pathogenic | 0.9478 | pathogenic | -1.053 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.472114529 | None | None | I |
| A/E | 0.8111 | likely_pathogenic | 0.8778 | pathogenic | -1.21 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| A/F | 0.827 | likely_pathogenic | 0.9131 | pathogenic | -1.198 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| A/G | 0.4688 | ambiguous | 0.6028 | pathogenic | -0.616 | Destabilizing | 1.0 | D | 0.525 | neutral | N | 0.501828579 | None | None | I |
| A/H | 0.7692 | likely_pathogenic | 0.8542 | pathogenic | -0.749 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| A/I | 0.6466 | likely_pathogenic | 0.7339 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
| A/K | 0.7915 | likely_pathogenic | 0.8717 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| A/L | 0.6642 | likely_pathogenic | 0.7213 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| A/M | 0.6086 | likely_pathogenic | 0.7059 | pathogenic | -0.241 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| A/N | 0.705 | likely_pathogenic | 0.7904 | pathogenic | -0.424 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| A/P | 0.9563 | likely_pathogenic | 0.973 | pathogenic | -0.473 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.464517205 | None | None | I |
| A/Q | 0.6487 | likely_pathogenic | 0.7115 | pathogenic | -0.779 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| A/R | 0.661 | likely_pathogenic | 0.7432 | pathogenic | -0.311 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| A/S | 0.1398 | likely_benign | 0.1819 | benign | -0.574 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.456376904 | None | None | I |
| A/T | 0.2724 | likely_benign | 0.3405 | ambiguous | -0.667 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.515430136 | None | None | I |
| A/V | 0.2907 | likely_benign | 0.3736 | ambiguous | -0.473 | Destabilizing | 1.0 | D | 0.614 | neutral | N | 0.506077147 | None | None | I |
| A/W | 0.9671 | likely_pathogenic | 0.9824 | pathogenic | -1.352 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| A/Y | 0.8803 | likely_pathogenic | 0.9375 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.809 | deleterious | 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.