Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13723 | 41392;41393;41394 | chr2:178636560;178636559;178636558 | chr2:179501287;179501286;179501285 |
| N2AB | 12082 | 36469;36470;36471 | chr2:178636560;178636559;178636558 | chr2:179501287;179501286;179501285 |
| N2A | 11155 | 33688;33689;33690 | chr2:178636560;178636559;178636558 | chr2:179501287;179501286;179501285 |
| N2B | 4658 | 14197;14198;14199 | chr2:178636560;178636559;178636558 | chr2:179501287;179501286;179501285 |
| Novex-1 | 4783 | 14572;14573;14574 | chr2:178636560;178636559;178636558 | chr2:179501287;179501286;179501285 |
| Novex-2 | 4850 | 14773;14774;14775 | chr2:178636560;178636559;178636558 | chr2:179501287;179501286;179501285 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | None | None | 1.0 | N | 0.673 | 0.435 | 0.32306181527 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| G/S | rs188301588  |
-0.467 | 1.0 | D | 0.7 | 0.536 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 6.24E-05 | 0 |
| G/S | rs188301588 |
-0.467 | 1.0 | D | 0.7 | 0.536 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.87747E-04 | None | 0 | 0 | 0 | 0 | 0 |
| G/S | rs188301588 |
-0.467 | 1.0 | D | 0.7 | 0.536 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| G/S | rs188301588 |
-0.467 | 1.0 | D | 0.7 | 0.536 | None | gnomAD-4.0.0 | 1.85937E-05 | None | None | None | None | N | None | 0 | 1.6675E-05 | None | 0 | 6.70151E-05 | None | 0 | 0 | 1.94981E-05 | 3.29424E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.5418 | ambiguous | 0.7087 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.603 | neutral | D | 0.599677426 | None | None | N |
| G/C | 0.7829 | likely_pathogenic | 0.8987 | pathogenic | -0.765 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | D | 0.647861015 | None | None | N |
| G/D | 0.4769 | ambiguous | 0.5838 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.453955442 | None | None | N |
| G/E | 0.6827 | likely_pathogenic | 0.8312 | pathogenic | -0.915 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| G/F | 0.9642 | likely_pathogenic | 0.9862 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| G/H | 0.8074 | likely_pathogenic | 0.9079 | pathogenic | -0.402 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| G/I | 0.9334 | likely_pathogenic | 0.9734 | pathogenic | -0.46 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| G/K | 0.8117 | likely_pathogenic | 0.9114 | pathogenic | -0.64 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| G/L | 0.9443 | likely_pathogenic | 0.9751 | pathogenic | -0.46 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| G/M | 0.9438 | likely_pathogenic | 0.9762 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| G/N | 0.4813 | ambiguous | 0.5787 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| G/P | 0.9968 | likely_pathogenic | 0.999 | pathogenic | -0.345 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| G/Q | 0.718 | likely_pathogenic | 0.8451 | pathogenic | -0.632 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| G/R | 0.6809 | likely_pathogenic | 0.8508 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.582360439 | None | None | N |
| G/S | 0.2279 | likely_benign | 0.3379 | benign | -0.373 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | D | 0.556565354 | None | None | N |
| G/T | 0.676 | likely_pathogenic | 0.8202 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| G/V | 0.8851 | likely_pathogenic | 0.9527 | pathogenic | -0.345 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | D | 0.722858626 | None | None | N |
| G/W | 0.9358 | likely_pathogenic | 0.9762 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| G/Y | 0.9222 | likely_pathogenic | 0.968 | pathogenic | -0.861 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | 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.