Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14839 | 44740;44741;44742 | chr2:178625306;178625305;178625304 | chr2:179490033;179490032;179490031 |
| N2AB | 13198 | 39817;39818;39819 | chr2:178625306;178625305;178625304 | chr2:179490033;179490032;179490031 |
| N2A | 12271 | 37036;37037;37038 | chr2:178625306;178625305;178625304 | chr2:179490033;179490032;179490031 |
| N2B | 5774 | 17545;17546;17547 | chr2:178625306;178625305;178625304 | chr2:179490033;179490032;179490031 |
| Novex-1 | 5899 | 17920;17921;17922 | chr2:178625306;178625305;178625304 | chr2:179490033;179490032;179490031 |
| Novex-2 | 5966 | 18121;18122;18123 | chr2:178625306;178625305;178625304 | chr2:179490033;179490032;179490031 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs753336110  |
-0.261 | 1.0 | N | 0.53 | 0.347 | 0.165133752707 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.36E-05 | None | 0 | 0 | 0 |
| D/N | rs753336110 |
-0.261 | 1.0 | N | 0.53 | 0.347 | 0.165133752707 | gnomAD-4.0.0 | 6.86916E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1708E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5109 | ambiguous | 0.5832 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.673 | neutral | N | 0.435277064 | None | None | N |
| D/C | 0.9354 | likely_pathogenic | 0.954 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/E | 0.4936 | ambiguous | 0.5141 | ambiguous | -0.346 | Destabilizing | 1.0 | D | 0.385 | neutral | N | 0.429708563 | None | None | N |
| D/F | 0.8859 | likely_pathogenic | 0.9078 | pathogenic | -0.098 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/G | 0.3605 | ambiguous | 0.4142 | ambiguous | -0.078 | Destabilizing | 1.0 | D | 0.579 | neutral | N | 0.443283714 | None | None | N |
| D/H | 0.7263 | likely_pathogenic | 0.7808 | pathogenic | 0.551 | Stabilizing | 1.0 | D | 0.597 | neutral | N | 0.478676647 | None | None | N |
| D/I | 0.7652 | likely_pathogenic | 0.8301 | pathogenic | 0.21 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/K | 0.8489 | likely_pathogenic | 0.8849 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | N |
| D/L | 0.7952 | likely_pathogenic | 0.8419 | pathogenic | 0.21 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/M | 0.9181 | likely_pathogenic | 0.9386 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/N | 0.2354 | likely_benign | 0.2801 | benign | 0.142 | Stabilizing | 1.0 | D | 0.53 | neutral | N | 0.437056892 | None | None | N |
| D/P | 0.9368 | likely_pathogenic | 0.9449 | pathogenic | 0.165 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| D/Q | 0.8008 | likely_pathogenic | 0.8399 | pathogenic | 0.134 | Stabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| D/R | 0.848 | likely_pathogenic | 0.884 | pathogenic | 0.586 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/S | 0.4066 | ambiguous | 0.4614 | ambiguous | 0.036 | Stabilizing | 1.0 | D | 0.546 | neutral | None | None | None | None | N |
| D/T | 0.6287 | likely_pathogenic | 0.6856 | pathogenic | 0.118 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| D/V | 0.5762 | likely_pathogenic | 0.6694 | pathogenic | 0.165 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.555026049 | None | None | N |
| D/W | 0.9765 | likely_pathogenic | 0.9815 | pathogenic | -0.073 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4586 | ambiguous | 0.5278 | ambiguous | 0.119 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | D | 0.55789792 | 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.