Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33635 | 101128;101129;101130 | chr2:178535712;178535711;178535710 | chr2:179400439;179400438;179400437 |
| N2AB | 31994 | 96205;96206;96207 | chr2:178535712;178535711;178535710 | chr2:179400439;179400438;179400437 |
| N2A | 31067 | 93424;93425;93426 | chr2:178535712;178535711;178535710 | chr2:179400439;179400438;179400437 |
| N2B | 24570 | 73933;73934;73935 | chr2:178535712;178535711;178535710 | chr2:179400439;179400438;179400437 |
| Novex-1 | 24695 | 74308;74309;74310 | chr2:178535712;178535711;178535710 | chr2:179400439;179400438;179400437 |
| Novex-2 | 24762 | 74509;74510;74511 | chr2:178535712;178535711;178535710 | chr2:179400439;179400438;179400437 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs879048474  |
-0.666 | 0.999 | D | 0.703 | 0.213 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| L/F | rs879048474 |
-0.666 | 0.999 | D | 0.703 | 0.213 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs879048474 |
-0.666 | 0.999 | D | 0.703 | 0.213 | None | gnomAD-4.0.0 | 4.33796E-06 | None | None | None | None | N | None | 1.33522E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08569E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7688 | likely_pathogenic | 0.5391 | ambiguous | -0.599 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| L/C | 0.9348 | likely_pathogenic | 0.8342 | pathogenic | -0.488 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/D | 0.9709 | likely_pathogenic | 0.9129 | pathogenic | -0.126 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/E | 0.8984 | likely_pathogenic | 0.7584 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/F | 0.5503 | ambiguous | 0.3766 | ambiguous | -0.696 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | D | 0.52778701 | None | None | N |
| L/G | 0.9536 | likely_pathogenic | 0.8845 | pathogenic | -0.761 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| L/H | 0.8058 | likely_pathogenic | 0.6019 | pathogenic | -0.139 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.527266935 | None | None | N |
| L/I | 0.1815 | likely_benign | 0.117 | benign | -0.302 | Destabilizing | 0.193 | N | 0.267 | neutral | N | 0.463236886 | None | None | N |
| L/K | 0.8177 | likely_pathogenic | 0.6339 | pathogenic | -0.229 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/M | 0.2618 | likely_benign | 0.185 | benign | -0.258 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| L/N | 0.8573 | likely_pathogenic | 0.6839 | pathogenic | 0.041 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| L/P | 0.922 | likely_pathogenic | 0.7228 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | N | 0.436471573 | None | None | N |
| L/Q | 0.7256 | likely_pathogenic | 0.5031 | ambiguous | -0.218 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/R | 0.7573 | likely_pathogenic | 0.5654 | pathogenic | 0.313 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | N | 0.474048526 | None | None | N |
| L/S | 0.8771 | likely_pathogenic | 0.6875 | pathogenic | -0.417 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| L/T | 0.6622 | likely_pathogenic | 0.4317 | ambiguous | -0.412 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| L/V | 0.2307 | likely_benign | 0.1434 | benign | -0.367 | Destabilizing | 0.829 | D | 0.537 | neutral | N | 0.441533463 | None | None | N |
| L/W | 0.8341 | likely_pathogenic | 0.7081 | pathogenic | -0.708 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/Y | 0.853 | likely_pathogenic | 0.7394 | pathogenic | -0.435 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | 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.