Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14035 | 42328;42329;42330 | chr2:178634771;178634770;178634769 | chr2:179499498;179499497;179499496 |
| N2AB | 12394 | 37405;37406;37407 | chr2:178634771;178634770;178634769 | chr2:179499498;179499497;179499496 |
| N2A | 11467 | 34624;34625;34626 | chr2:178634771;178634770;178634769 | chr2:179499498;179499497;179499496 |
| N2B | 4970 | 15133;15134;15135 | chr2:178634771;178634770;178634769 | chr2:179499498;179499497;179499496 |
| Novex-1 | 5095 | 15508;15509;15510 | chr2:178634771;178634770;178634769 | chr2:179499498;179499497;179499496 |
| Novex-2 | 5162 | 15709;15710;15711 | chr2:178634771;178634770;178634769 | chr2:179499498;179499497;179499496 |
| 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 | rs1433887768  |
-1.584 | 0.771 | N | 0.655 | 0.107 | 0.29385284311 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.89E-06 | 0 |
| L/F | rs1433887768 |
-1.584 | 0.771 | N | 0.655 | 0.107 | 0.29385284311 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07469E-04 | 0 |
| L/F | rs1433887768 |
-1.584 | 0.771 | N | 0.655 | 0.107 | 0.29385284311 | gnomAD-4.0.0 | 8.05933E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4786E-06 | 3.29583E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3471 | ambiguous | 0.2308 | benign | -2.37 | Highly Destabilizing | 0.115 | N | 0.612 | neutral | None | None | None | None | N |
| L/C | 0.6431 | likely_pathogenic | 0.5665 | pathogenic | -1.731 | Destabilizing | 0.944 | D | 0.691 | prob.delet. | None | None | None | None | N |
| L/D | 0.9228 | likely_pathogenic | 0.8473 | pathogenic | -2.388 | Highly Destabilizing | 0.687 | D | 0.677 | prob.neutral | None | None | None | None | N |
| L/E | 0.6386 | likely_pathogenic | 0.4523 | ambiguous | -2.199 | Highly Destabilizing | 0.239 | N | 0.692 | prob.delet. | None | None | None | None | N |
| L/F | 0.2711 | likely_benign | 0.1891 | benign | -1.352 | Destabilizing | 0.771 | D | 0.655 | prob.neutral | N | 0.437168709 | None | None | N |
| L/G | 0.7719 | likely_pathogenic | 0.6604 | pathogenic | -2.882 | Highly Destabilizing | 0.239 | N | 0.731 | deleterious | None | None | None | None | N |
| L/H | 0.4598 | ambiguous | 0.3072 | benign | -2.21 | Highly Destabilizing | 0.927 | D | 0.723 | deleterious | N | 0.430912281 | None | None | N |
| L/I | 0.1526 | likely_benign | 0.1021 | benign | -0.916 | Destabilizing | 0.321 | N | 0.662 | prob.neutral | N | 0.424740945 | None | None | N |
| L/K | 0.6548 | likely_pathogenic | 0.5089 | ambiguous | -1.707 | Destabilizing | 0.239 | N | 0.71 | prob.delet. | None | None | None | None | N |
| L/M | 0.1376 | likely_benign | 0.1035 | benign | -0.964 | Destabilizing | 0.931 | D | 0.667 | prob.neutral | None | None | None | None | N |
| L/N | 0.6091 | likely_pathogenic | 0.4493 | ambiguous | -1.927 | Destabilizing | 0.524 | D | 0.681 | prob.neutral | None | None | None | None | N |
| L/P | 0.9943 | likely_pathogenic | 0.9894 | pathogenic | -1.379 | Destabilizing | 0.771 | D | 0.695 | prob.delet. | N | 0.43850021 | None | None | N |
| L/Q | 0.2842 | likely_benign | 0.1812 | benign | -1.856 | Destabilizing | 0.687 | D | 0.684 | prob.delet. | None | None | None | None | N |
| L/R | 0.5657 | likely_pathogenic | 0.4207 | ambiguous | -1.369 | Destabilizing | 0.624 | D | 0.65 | prob.neutral | N | 0.435554938 | None | None | N |
| L/S | 0.3343 | likely_benign | 0.2006 | benign | -2.66 | Highly Destabilizing | 0.001 | N | 0.605 | neutral | None | None | None | None | N |
| L/T | 0.224 | likely_benign | 0.1404 | benign | -2.331 | Highly Destabilizing | 0.239 | N | 0.713 | prob.delet. | None | None | None | None | N |
| L/V | 0.154 | likely_benign | 0.0994 | benign | -1.379 | Destabilizing | 0.321 | N | 0.681 | prob.neutral | N | 0.42809458 | None | None | N |
| L/W | 0.5999 | likely_pathogenic | 0.4932 | ambiguous | -1.657 | Destabilizing | 0.981 | D | 0.727 | deleterious | None | None | None | None | N |
| L/Y | 0.549 | ambiguous | 0.4549 | ambiguous | -1.382 | Destabilizing | 0.817 | D | 0.716 | 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.