Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19614 | 59065;59066;59067 | chr2:178593368;178593367;178593366 | chr2:179458095;179458094;179458093 |
| N2AB | 17973 | 54142;54143;54144 | chr2:178593368;178593367;178593366 | chr2:179458095;179458094;179458093 |
| N2A | 17046 | 51361;51362;51363 | chr2:178593368;178593367;178593366 | chr2:179458095;179458094;179458093 |
| N2B | 10549 | 31870;31871;31872 | chr2:178593368;178593367;178593366 | chr2:179458095;179458094;179458093 |
| Novex-1 | 10674 | 32245;32246;32247 | chr2:178593368;178593367;178593366 | chr2:179458095;179458094;179458093 |
| Novex-2 | 10741 | 32446;32447;32448 | chr2:178593368;178593367;178593366 | chr2:179458095;179458094;179458093 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs199933004  |
-2.901 | 0.822 | N | 0.684 | 0.345 | None | gnomAD-2.1.1 | 8.04E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 1.59046E-03 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| I/T | rs199933004 |
-2.901 | 0.822 | N | 0.684 | 0.345 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 1.7301E-03 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs199933004 |
-2.901 | 0.822 | N | 0.684 | 0.345 | None | gnomAD-4.0.0 | 4.52525E-05 | None | None | None | None | N | None | 0 | 1.66834E-05 | None | 1.5887E-03 | 0 | None | 0 | 0 | 1.52599E-05 | 0 | 1.12108E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7039 | likely_pathogenic | 0.7117 | pathogenic | -2.253 | Highly Destabilizing | 0.754 | D | 0.661 | neutral | None | None | None | None | N |
| I/C | 0.6868 | likely_pathogenic | 0.705 | pathogenic | -1.361 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | N |
| I/D | 0.9329 | likely_pathogenic | 0.9177 | pathogenic | -1.937 | Destabilizing | 0.993 | D | 0.798 | deleterious | None | None | None | None | N |
| I/E | 0.8651 | likely_pathogenic | 0.8502 | pathogenic | -1.845 | Destabilizing | 0.978 | D | 0.784 | deleterious | None | None | None | None | N |
| I/F | 0.1376 | likely_benign | 0.1342 | benign | -1.389 | Destabilizing | 0.942 | D | 0.697 | prob.neutral | N | 0.469456227 | None | None | N |
| I/G | 0.8994 | likely_pathogenic | 0.9017 | pathogenic | -2.678 | Highly Destabilizing | 0.978 | D | 0.775 | deleterious | None | None | None | None | N |
| I/H | 0.4796 | ambiguous | 0.4544 | ambiguous | -1.81 | Destabilizing | 0.998 | D | 0.766 | deleterious | None | None | None | None | N |
| I/K | 0.648 | likely_pathogenic | 0.5926 | pathogenic | -1.728 | Destabilizing | 0.978 | D | 0.784 | deleterious | None | None | None | None | N |
| I/L | 0.1368 | likely_benign | 0.1374 | benign | -1.095 | Destabilizing | 0.294 | N | 0.473 | neutral | N | 0.494140505 | None | None | N |
| I/M | 0.1792 | likely_benign | 0.1798 | benign | -0.827 | Destabilizing | 0.942 | D | 0.715 | prob.delet. | N | 0.484370931 | None | None | N |
| I/N | 0.4927 | ambiguous | 0.4745 | ambiguous | -1.671 | Destabilizing | 0.99 | D | 0.801 | deleterious | N | 0.468998474 | None | None | N |
| I/P | 0.9919 | likely_pathogenic | 0.9883 | pathogenic | -1.455 | Destabilizing | 0.993 | D | 0.802 | deleterious | None | None | None | None | N |
| I/Q | 0.6414 | likely_pathogenic | 0.6264 | pathogenic | -1.759 | Destabilizing | 0.993 | D | 0.789 | deleterious | None | None | None | None | N |
| I/R | 0.5064 | ambiguous | 0.4545 | ambiguous | -1.122 | Destabilizing | 0.978 | D | 0.801 | deleterious | None | None | None | None | N |
| I/S | 0.5697 | likely_pathogenic | 0.5586 | ambiguous | -2.352 | Highly Destabilizing | 0.942 | D | 0.695 | prob.neutral | N | 0.472503966 | None | None | N |
| I/T | 0.4624 | ambiguous | 0.448 | ambiguous | -2.137 | Highly Destabilizing | 0.822 | D | 0.684 | prob.neutral | N | 0.505376219 | None | None | N |
| I/V | 0.0943 | likely_benign | 0.0982 | benign | -1.455 | Destabilizing | 0.006 | N | 0.265 | neutral | N | 0.475093384 | None | None | N |
| I/W | 0.7008 | likely_pathogenic | 0.7077 | pathogenic | -1.558 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/Y | 0.3697 | ambiguous | 0.3659 | ambiguous | -1.355 | Destabilizing | 0.978 | D | 0.711 | 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.