Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16782 | 50569;50570;50571 | chr2:178612067;178612066;178612065 | chr2:179476794;179476793;179476792 |
| N2AB | 15141 | 45646;45647;45648 | chr2:178612067;178612066;178612065 | chr2:179476794;179476793;179476792 |
| N2A | 14214 | 42865;42866;42867 | chr2:178612067;178612066;178612065 | chr2:179476794;179476793;179476792 |
| N2B | 7717 | 23374;23375;23376 | chr2:178612067;178612066;178612065 | chr2:179476794;179476793;179476792 |
| Novex-1 | 7842 | 23749;23750;23751 | chr2:178612067;178612066;178612065 | chr2:179476794;179476793;179476792 |
| Novex-2 | 7909 | 23950;23951;23952 | chr2:178612067;178612066;178612065 | chr2:179476794;179476793;179476792 |
| 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 | rs761148844  |
None | 1.0 | N | 0.678 | 0.365 | 0.390531646278 | gnomAD-4.0.0 | 6.1708E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.20382E-06 | 0 | 1.66036E-05 |
| P/T | rs761148844 |
-0.448 | 1.0 | D | 0.744 | 0.467 | 0.453679287548 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.03E-06 | 0 |
| P/T | rs761148844 |
-0.448 | 1.0 | D | 0.744 | 0.467 | 0.453679287548 | gnomAD-4.0.0 | 6.85644E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00477E-07 | 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 | 0.1355 | likely_benign | 0.1527 | benign | -0.854 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | N | 0.504519002 | None | None | I |
| P/C | 0.7752 | likely_pathogenic | 0.8229 | pathogenic | -0.582 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| P/D | 0.6738 | likely_pathogenic | 0.6789 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| P/E | 0.4707 | ambiguous | 0.4925 | ambiguous | -0.884 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| P/F | 0.7866 | likely_pathogenic | 0.8421 | pathogenic | -0.974 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
| P/G | 0.5446 | ambiguous | 0.5948 | pathogenic | -1.035 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| P/H | 0.4029 | ambiguous | 0.472 | ambiguous | -0.6 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| P/I | 0.5193 | ambiguous | 0.5735 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| P/K | 0.4863 | ambiguous | 0.5294 | ambiguous | -0.74 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/L | 0.2391 | likely_benign | 0.2769 | benign | -0.511 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | D | 0.604108157 | None | None | I |
| P/M | 0.5401 | ambiguous | 0.5809 | pathogenic | -0.339 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| P/N | 0.5738 | likely_pathogenic | 0.5949 | pathogenic | -0.376 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/Q | 0.2906 | likely_benign | 0.3423 | ambiguous | -0.672 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.589970167 | None | None | I |
| P/R | 0.3573 | ambiguous | 0.4519 | ambiguous | -0.126 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.550646089 | None | None | I |
| P/S | 0.262 | likely_benign | 0.3087 | benign | -0.741 | Destabilizing | 1.0 | D | 0.759 | deleterious | D | 0.548457965 | None | None | I |
| P/T | 0.2204 | likely_benign | 0.2657 | benign | -0.752 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.573246568 | None | None | I |
| P/V | 0.3758 | ambiguous | 0.4155 | ambiguous | -0.59 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| P/W | 0.906 | likely_pathogenic | 0.9367 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| P/Y | 0.7378 | likely_pathogenic | 0.7992 | pathogenic | -0.775 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | 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.