Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32232 | 96919;96920;96921 | chr2:178543279;178543278;178543277 | chr2:179408006;179408005;179408004 |
| N2AB | 30591 | 91996;91997;91998 | chr2:178543279;178543278;178543277 | chr2:179408006;179408005;179408004 |
| N2A | 29664 | 89215;89216;89217 | chr2:178543279;178543278;178543277 | chr2:179408006;179408005;179408004 |
| N2B | 23167 | 69724;69725;69726 | chr2:178543279;178543278;178543277 | chr2:179408006;179408005;179408004 |
| Novex-1 | 23292 | 70099;70100;70101 | chr2:178543279;178543278;178543277 | chr2:179408006;179408005;179408004 |
| Novex-2 | 23359 | 70300;70301;70302 | chr2:178543279;178543278;178543277 | chr2:179408006;179408005;179408004 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs748359406  |
-0.579 | 1.0 | N | 0.622 | 0.528 | 0.437634105008 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65673E-04 |
| S/R | rs748359406 |
-0.579 | 1.0 | N | 0.622 | 0.528 | 0.437634105008 | gnomAD-4.0.0 | 1.59112E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02352E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1594 | likely_benign | 0.1773 | benign | -0.573 | Destabilizing | 0.315 | N | 0.637 | neutral | None | None | None | None | I |
| S/C | 0.1394 | likely_benign | 0.1409 | benign | -0.42 | Destabilizing | 1.0 | D | 0.61 | neutral | N | 0.477969058 | None | None | I |
| S/D | 0.8809 | likely_pathogenic | 0.889 | pathogenic | -0.647 | Destabilizing | 0.854 | D | 0.607 | neutral | None | None | None | None | I |
| S/E | 0.8981 | likely_pathogenic | 0.9154 | pathogenic | -0.693 | Destabilizing | 0.943 | D | 0.631 | neutral | None | None | None | None | I |
| S/F | 0.5633 | ambiguous | 0.5878 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| S/G | 0.189 | likely_benign | 0.2495 | benign | -0.767 | Destabilizing | 0.943 | D | 0.596 | neutral | N | 0.463247574 | None | None | I |
| S/H | 0.6457 | likely_pathogenic | 0.6871 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | I |
| S/I | 0.5977 | likely_pathogenic | 0.6405 | pathogenic | -0.175 | Destabilizing | 0.999 | D | 0.668 | neutral | N | 0.497932964 | None | None | I |
| S/K | 0.911 | likely_pathogenic | 0.9471 | pathogenic | -0.778 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| S/L | 0.2608 | likely_benign | 0.2991 | benign | -0.175 | Destabilizing | 0.996 | D | 0.621 | neutral | None | None | None | None | I |
| S/M | 0.4407 | ambiguous | 0.4855 | ambiguous | 0.269 | Stabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | I |
| S/N | 0.4657 | ambiguous | 0.4815 | ambiguous | -0.673 | Destabilizing | 0.014 | N | 0.454 | neutral | N | 0.488716252 | None | None | I |
| S/P | 0.9669 | likely_pathogenic | 0.979 | pathogenic | -0.276 | Destabilizing | 0.988 | D | 0.622 | neutral | None | None | None | None | I |
| S/Q | 0.7648 | likely_pathogenic | 0.8204 | pathogenic | -0.956 | Destabilizing | 0.997 | D | 0.653 | neutral | None | None | None | None | I |
| S/R | 0.8637 | likely_pathogenic | 0.9118 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.622 | neutral | N | 0.492284197 | None | None | I |
| S/T | 0.186 | likely_benign | 0.221 | benign | -0.664 | Destabilizing | 0.001 | N | 0.436 | neutral | N | 0.481056476 | None | None | I |
| S/V | 0.4987 | ambiguous | 0.5387 | ambiguous | -0.276 | Destabilizing | 0.997 | D | 0.627 | neutral | None | None | None | None | I |
| S/W | 0.6859 | likely_pathogenic | 0.7218 | pathogenic | -0.926 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| S/Y | 0.5225 | ambiguous | 0.5625 | ambiguous | -0.661 | Destabilizing | 1.0 | D | 0.659 | 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.