Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3018 | 9277;9278;9279 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
| N2AB | 3018 | 9277;9278;9279 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
| N2A | 3018 | 9277;9278;9279 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
| N2B | 2972 | 9139;9140;9141 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
| Novex-1 | 2972 | 9139;9140;9141 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
| Novex-2 | 2972 | 9139;9140;9141 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
| Novex-3 | 3018 | 9277;9278;9279 | chr2:178768784;178768783;178768782 | chr2:179633511;179633510;179633509 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs761555504  |
-0.009 | 0.901 | N | 0.649 | 0.341 | 0.457741393631 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| T/I | rs761555504 |
-0.009 | 0.901 | N | 0.649 | 0.341 | 0.457741393631 | gnomAD-4.0.0 | 3.18116E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71298E-06 | 0 | 0 |
| T/N | rs761555504 |
-0.258 | 0.901 | N | 0.627 | 0.235 | 0.407632638399 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| T/N | rs761555504 |
-0.258 | 0.901 | N | 0.627 | 0.235 | 0.407632638399 | gnomAD-4.0.0 | 3.18117E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86549E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1386 | likely_benign | 0.1569 | benign | -0.796 | Destabilizing | 0.008 | N | 0.294 | neutral | N | 0.413844252 | None | None | N |
| T/C | 0.54 | ambiguous | 0.6362 | pathogenic | -0.354 | Destabilizing | 0.989 | D | 0.66 | neutral | None | None | None | None | N |
| T/D | 0.6956 | likely_pathogenic | 0.7607 | pathogenic | 0.051 | Stabilizing | 0.923 | D | 0.622 | neutral | None | None | None | None | N |
| T/E | 0.576 | likely_pathogenic | 0.6138 | pathogenic | 0.027 | Stabilizing | 0.775 | D | 0.617 | neutral | None | None | None | None | N |
| T/F | 0.5583 | ambiguous | 0.635 | pathogenic | -1.029 | Destabilizing | 0.961 | D | 0.732 | prob.delet. | None | None | None | None | N |
| T/G | 0.447 | ambiguous | 0.5282 | ambiguous | -1.018 | Destabilizing | 0.633 | D | 0.669 | neutral | None | None | None | None | N |
| T/H | 0.435 | ambiguous | 0.537 | ambiguous | -1.321 | Destabilizing | 0.996 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/I | 0.3793 | ambiguous | 0.4135 | ambiguous | -0.306 | Destabilizing | 0.901 | D | 0.649 | neutral | N | 0.473414809 | None | None | N |
| T/K | 0.4224 | ambiguous | 0.4863 | ambiguous | -0.608 | Destabilizing | 0.775 | D | 0.619 | neutral | None | None | None | None | N |
| T/L | 0.2932 | likely_benign | 0.2995 | benign | -0.306 | Destabilizing | 0.633 | D | 0.613 | neutral | None | None | None | None | N |
| T/M | 0.1479 | likely_benign | 0.1644 | benign | 0.018 | Stabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | N |
| T/N | 0.2164 | likely_benign | 0.2631 | benign | -0.439 | Destabilizing | 0.901 | D | 0.627 | neutral | N | 0.489183726 | None | None | N |
| T/P | 0.4569 | ambiguous | 0.5021 | ambiguous | -0.438 | Destabilizing | 0.949 | D | 0.654 | neutral | N | 0.504786338 | None | None | N |
| T/Q | 0.3419 | ambiguous | 0.392 | ambiguous | -0.611 | Destabilizing | 0.961 | D | 0.658 | neutral | None | None | None | None | N |
| T/R | 0.3788 | ambiguous | 0.4265 | ambiguous | -0.383 | Destabilizing | 0.923 | D | 0.655 | neutral | None | None | None | None | N |
| T/S | 0.14 | likely_benign | 0.178 | benign | -0.727 | Destabilizing | 0.092 | N | 0.274 | neutral | N | 0.413122556 | None | None | N |
| T/V | 0.2558 | likely_benign | 0.2753 | benign | -0.438 | Destabilizing | 0.633 | D | 0.605 | neutral | None | None | None | None | N |
| T/W | 0.8327 | likely_pathogenic | 0.8892 | pathogenic | -0.967 | Destabilizing | 0.996 | D | 0.744 | deleterious | None | None | None | None | N |
| T/Y | 0.5554 | ambiguous | 0.6612 | pathogenic | -0.734 | Destabilizing | 0.987 | D | 0.729 | 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.