Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1923 | 5992;5993;5994 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
| N2AB | 1923 | 5992;5993;5994 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
| N2A | 1923 | 5992;5993;5994 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
| N2B | 1877 | 5854;5855;5856 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
| Novex-1 | 1877 | 5854;5855;5856 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
| Novex-2 | 1877 | 5854;5855;5856 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
| Novex-3 | 1923 | 5992;5993;5994 | chr2:178776097;178776096;178776095 | chr2:179640824;179640823;179640822 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/Q | None | None | 1.0 | N | 0.742 | 0.354 | 0.37550373646 | gnomAD-4.0.0 | 1.36814E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7986E-06 | 0 | 0 |
| H/R | None | None | 1.0 | N | 0.698 | 0.616 | 0.425148423609 | gnomAD-4.0.0 | 3.18103E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86541E-05 | 0 |
| H/Y | None | None | 0.999 | N | 0.577 | 0.591 | 0.384419519794 | gnomAD-4.0.0 | 1.59051E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85656E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.6482 | likely_pathogenic | 0.6424 | pathogenic | -1.509 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | I |
| H/C | 0.4007 | ambiguous | 0.3707 | ambiguous | -0.672 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| H/D | 0.6957 | likely_pathogenic | 0.7052 | pathogenic | -1.781 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.505843935 | None | None | I |
| H/E | 0.6064 | likely_pathogenic | 0.6036 | pathogenic | -1.612 | Destabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | I |
| H/F | 0.6155 | likely_pathogenic | 0.5747 | pathogenic | 0.308 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| H/G | 0.7413 | likely_pathogenic | 0.7516 | pathogenic | -1.915 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | I |
| H/I | 0.7793 | likely_pathogenic | 0.7388 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| H/K | 0.5788 | likely_pathogenic | 0.5823 | pathogenic | -1.117 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| H/L | 0.5228 | ambiguous | 0.486 | ambiguous | -0.323 | Destabilizing | 1.0 | D | 0.789 | deleterious | N | 0.497369495 | None | None | I |
| H/M | 0.8022 | likely_pathogenic | 0.7746 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| H/N | 0.2594 | likely_benign | 0.2418 | benign | -1.74 | Destabilizing | 0.999 | D | 0.561 | neutral | N | 0.501326296 | None | None | I |
| H/P | 0.9758 | likely_pathogenic | 0.9827 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.569756853 | None | None | I |
| H/Q | 0.3693 | ambiguous | 0.3435 | ambiguous | -1.426 | Destabilizing | 1.0 | D | 0.742 | deleterious | N | 0.497369495 | None | None | I |
| H/R | 0.3527 | ambiguous | 0.3407 | ambiguous | -1.518 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | N | 0.478364766 | None | None | I |
| H/S | 0.5263 | ambiguous | 0.5058 | ambiguous | -1.686 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| H/T | 0.6176 | likely_pathogenic | 0.5824 | pathogenic | -1.398 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| H/V | 0.6649 | likely_pathogenic | 0.6268 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| H/W | 0.6957 | likely_pathogenic | 0.6933 | pathogenic | 0.86 | Stabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | I |
| H/Y | 0.1862 | likely_benign | 0.173 | benign | 0.646 | Stabilizing | 0.999 | D | 0.577 | neutral | N | 0.504217862 | None | None | I |
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.