Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22427 | 67504;67505;67506 | chr2:178580008;178580007;178580006 | chr2:179444735;179444734;179444733 |
| N2AB | 20786 | 62581;62582;62583 | chr2:178580008;178580007;178580006 | chr2:179444735;179444734;179444733 |
| N2A | 19859 | 59800;59801;59802 | chr2:178580008;178580007;178580006 | chr2:179444735;179444734;179444733 |
| N2B | 13362 | 40309;40310;40311 | chr2:178580008;178580007;178580006 | chr2:179444735;179444734;179444733 |
| Novex-1 | 13487 | 40684;40685;40686 | chr2:178580008;178580007;178580006 | chr2:179444735;179444734;179444733 |
| Novex-2 | 13554 | 40885;40886;40887 | chr2:178580008;178580007;178580006 | chr2:179444735;179444734;179444733 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs770566210  |
-0.856 | 1.0 | D | 0.74 | 0.681 | 0.771532404752 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/Q | rs770566210 |
-1.163 | 1.0 | N | 0.79 | 0.542 | 0.28492961333 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/Q | rs770566210 |
-1.163 | 1.0 | N | 0.79 | 0.542 | 0.28492961333 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs770566210 |
-1.163 | 1.0 | N | 0.79 | 0.542 | 0.28492961333 | gnomAD-4.0.0 | 1.05381E-05 | None | None | None | None | N | None | 4.00673E-05 | 0 | None | 0 | 2.23334E-05 | None | 0 | 0 | 9.32591E-06 | 0 | 3.20359E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8788 | likely_pathogenic | 0.8754 | pathogenic | -2.055 | Highly Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| R/C | 0.4479 | ambiguous | 0.4046 | ambiguous | -1.868 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| R/D | 0.9936 | likely_pathogenic | 0.9923 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/E | 0.9113 | likely_pathogenic | 0.8989 | pathogenic | -1.114 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/F | 0.9842 | likely_pathogenic | 0.9805 | pathogenic | -1.068 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| R/G | 0.9059 | likely_pathogenic | 0.8999 | pathogenic | -2.374 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.552502899 | None | None | N |
| R/H | 0.484 | ambiguous | 0.4471 | ambiguous | -2.088 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| R/I | 0.886 | likely_pathogenic | 0.8694 | pathogenic | -1.11 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| R/K | 0.4022 | ambiguous | 0.3909 | ambiguous | -1.263 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| R/L | 0.8278 | likely_pathogenic | 0.8157 | pathogenic | -1.11 | Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.532183372 | None | None | N |
| R/M | 0.8406 | likely_pathogenic | 0.8259 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/N | 0.9707 | likely_pathogenic | 0.9691 | pathogenic | -1.525 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/P | 0.9987 | likely_pathogenic | 0.9987 | pathogenic | -1.418 | Destabilizing | 1.0 | D | 0.81 | deleterious | D | 0.564366184 | None | None | N |
| R/Q | 0.2767 | likely_benign | 0.2615 | benign | -1.258 | Destabilizing | 1.0 | D | 0.79 | deleterious | N | 0.494022624 | None | None | N |
| R/S | 0.9216 | likely_pathogenic | 0.9179 | pathogenic | -2.255 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/T | 0.893 | likely_pathogenic | 0.8806 | pathogenic | -1.836 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/V | 0.8968 | likely_pathogenic | 0.8812 | pathogenic | -1.418 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/W | 0.876 | likely_pathogenic | 0.8568 | pathogenic | -0.689 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/Y | 0.9462 | likely_pathogenic | 0.9311 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.833 | deleterious | 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.