Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16654 | 50185;50186;50187 | chr2:178612565;178612564;178612563 | chr2:179477292;179477291;179477290 |
| N2AB | 15013 | 45262;45263;45264 | chr2:178612565;178612564;178612563 | chr2:179477292;179477291;179477290 |
| N2A | 14086 | 42481;42482;42483 | chr2:178612565;178612564;178612563 | chr2:179477292;179477291;179477290 |
| N2B | 7589 | 22990;22991;22992 | chr2:178612565;178612564;178612563 | chr2:179477292;179477291;179477290 |
| Novex-1 | 7714 | 23365;23366;23367 | chr2:178612565;178612564;178612563 | chr2:179477292;179477291;179477290 |
| Novex-2 | 7781 | 23566;23567;23568 | chr2:178612565;178612564;178612563 | chr2:179477292;179477291;179477290 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs1362265469  |
-1.498 | 0.025 | N | 0.429 | 0.174 | 0.130388298395 | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | N | None | 0 | 3E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/A | rs1362265469 |
-1.498 | 0.025 | N | 0.429 | 0.174 | 0.130388298395 | gnomAD-4.0.0 | 1.60804E-06 | None | None | None | None | N | None | 0 | 2.34313E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1362265469 |
-1.598 | 0.698 | D | 0.765 | 0.298 | 0.208816687407 | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.38E-06 | 0 |
| P/S | rs1362265469 |
-1.598 | 0.698 | D | 0.765 | 0.298 | 0.208816687407 | gnomAD-4.0.0 | 1.60804E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87247E-06 | 0 | 0 |
| P/T | None | None | 0.032 | D | 0.517 | 0.286 | 0.285316908763 | gnomAD-4.0.0 | 6.43217E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11882E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1191 | likely_benign | 0.117 | benign | -1.498 | Destabilizing | 0.025 | N | 0.429 | neutral | N | 0.460624345 | None | None | N |
| P/C | 0.8269 | likely_pathogenic | 0.8368 | pathogenic | -1.192 | Destabilizing | 0.998 | D | 0.868 | deleterious | None | None | None | None | N |
| P/D | 0.9408 | likely_pathogenic | 0.9681 | pathogenic | -2.131 | Highly Destabilizing | 0.956 | D | 0.82 | deleterious | None | None | None | None | N |
| P/E | 0.7878 | likely_pathogenic | 0.8538 | pathogenic | -2.167 | Highly Destabilizing | 0.956 | D | 0.825 | deleterious | None | None | None | None | N |
| P/F | 0.9047 | likely_pathogenic | 0.9385 | pathogenic | -1.436 | Destabilizing | 0.978 | D | 0.893 | deleterious | None | None | None | None | N |
| P/G | 0.5591 | ambiguous | 0.5864 | pathogenic | -1.757 | Destabilizing | 0.86 | D | 0.825 | deleterious | None | None | None | None | N |
| P/H | 0.6531 | likely_pathogenic | 0.7545 | pathogenic | -1.23 | Destabilizing | 0.998 | D | 0.855 | deleterious | None | None | None | None | N |
| P/I | 0.8203 | likely_pathogenic | 0.8712 | pathogenic | -0.888 | Destabilizing | 0.956 | D | 0.889 | deleterious | None | None | None | None | N |
| P/K | 0.7032 | likely_pathogenic | 0.8178 | pathogenic | -1.176 | Destabilizing | 0.956 | D | 0.831 | deleterious | None | None | None | None | N |
| P/L | 0.5665 | likely_pathogenic | 0.6578 | pathogenic | -0.888 | Destabilizing | 0.698 | D | 0.85 | deleterious | D | 0.725563731 | None | None | N |
| P/M | 0.8176 | likely_pathogenic | 0.8405 | pathogenic | -0.649 | Destabilizing | 0.994 | D | 0.862 | deleterious | None | None | None | None | N |
| P/N | 0.8455 | likely_pathogenic | 0.893 | pathogenic | -1.075 | Destabilizing | 0.956 | D | 0.885 | deleterious | None | None | None | None | N |
| P/Q | 0.5126 | ambiguous | 0.5914 | pathogenic | -1.38 | Destabilizing | 0.97 | D | 0.797 | deleterious | D | 0.566888814 | None | None | N |
| P/R | 0.5722 | likely_pathogenic | 0.7002 | pathogenic | -0.57 | Destabilizing | 0.942 | D | 0.883 | deleterious | D | 0.625485777 | None | None | N |
| P/S | 0.2936 | likely_benign | 0.3395 | benign | -1.468 | Destabilizing | 0.698 | D | 0.765 | deleterious | D | 0.564008785 | None | None | N |
| P/T | 0.4403 | ambiguous | 0.5139 | ambiguous | -1.413 | Destabilizing | 0.032 | N | 0.517 | neutral | D | 0.617826442 | None | None | N |
| P/V | 0.6729 | likely_pathogenic | 0.7247 | pathogenic | -1.06 | Destabilizing | 0.754 | D | 0.841 | deleterious | None | None | None | None | N |
| P/W | 0.972 | likely_pathogenic | 0.983 | pathogenic | -1.584 | Destabilizing | 0.998 | D | 0.848 | deleterious | None | None | None | None | N |
| P/Y | 0.9002 | likely_pathogenic | 0.9411 | pathogenic | -1.28 | Destabilizing | 0.993 | D | 0.893 | deleterious | 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.