Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33604 | 101035;101036;101037 | chr2:178535805;178535804;178535803 | chr2:179400532;179400531;179400530 |
| N2AB | 31963 | 96112;96113;96114 | chr2:178535805;178535804;178535803 | chr2:179400532;179400531;179400530 |
| N2A | 31036 | 93331;93332;93333 | chr2:178535805;178535804;178535803 | chr2:179400532;179400531;179400530 |
| N2B | 24539 | 73840;73841;73842 | chr2:178535805;178535804;178535803 | chr2:179400532;179400531;179400530 |
| Novex-1 | 24664 | 74215;74216;74217 | chr2:178535805;178535804;178535803 | chr2:179400532;179400531;179400530 |
| Novex-2 | 24731 | 74416;74417;74418 | chr2:178535805;178535804;178535803 | chr2:179400532;179400531;179400530 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | None | None | 1.0 | N | 0.68 | 0.308 | 0.425499470309 | gnomAD-4.0.0 | 1.37344E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.92478E-05 | 0 | 0 | 0 | 1.6619E-05 |
| A/V | rs1691172442  |
None | 1.0 | N | 0.608 | 0.33 | 0.481393932785 | gnomAD-3.1.2 | 6.62E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs1691172442 |
None | 1.0 | N | 0.608 | 0.33 | 0.481393932785 | gnomAD-4.0.0 | 2.48809E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3982E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7088 | likely_pathogenic | 0.6053 | pathogenic | -0.685 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| A/D | 0.8132 | likely_pathogenic | 0.7081 | pathogenic | -1.181 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| A/E | 0.7342 | likely_pathogenic | 0.5988 | pathogenic | -1.288 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.443508535 | None | None | N |
| A/F | 0.7213 | likely_pathogenic | 0.5895 | pathogenic | -1.167 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| A/G | 0.325 | likely_benign | 0.2557 | benign | -0.98 | Destabilizing | 0.999 | D | 0.512 | neutral | N | 0.435235769 | None | None | N |
| A/H | 0.8112 | likely_pathogenic | 0.7055 | pathogenic | -1.176 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| A/I | 0.6658 | likely_pathogenic | 0.5097 | ambiguous | -0.541 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/K | 0.8163 | likely_pathogenic | 0.6846 | pathogenic | -1.166 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| A/L | 0.5648 | likely_pathogenic | 0.4232 | ambiguous | -0.541 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| A/M | 0.5797 | likely_pathogenic | 0.451 | ambiguous | -0.332 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/N | 0.6417 | likely_pathogenic | 0.5264 | ambiguous | -0.7 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/P | 0.5716 | likely_pathogenic | 0.4777 | ambiguous | -0.595 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.416129933 | None | None | N |
| A/Q | 0.6957 | likely_pathogenic | 0.5718 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| A/R | 0.7299 | likely_pathogenic | 0.5983 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| A/S | 0.1554 | likely_benign | 0.1369 | benign | -0.916 | Destabilizing | 0.998 | D | 0.524 | neutral | N | 0.418783449 | None | None | N |
| A/T | 0.2387 | likely_benign | 0.1818 | benign | -0.953 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.404720861 | None | None | N |
| A/V | 0.3714 | ambiguous | 0.2643 | benign | -0.595 | Destabilizing | 1.0 | D | 0.608 | neutral | N | 0.470599136 | None | None | N |
| A/W | 0.9552 | likely_pathogenic | 0.9153 | pathogenic | -1.399 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/Y | 0.8454 | likely_pathogenic | 0.7389 | pathogenic | -1.064 | Destabilizing | 1.0 | D | 0.82 | 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.