Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14829 | 44710;44711;44712 | chr2:178625336;178625335;178625334 | chr2:179490063;179490062;179490061 |
| N2AB | 13188 | 39787;39788;39789 | chr2:178625336;178625335;178625334 | chr2:179490063;179490062;179490061 |
| N2A | 12261 | 37006;37007;37008 | chr2:178625336;178625335;178625334 | chr2:179490063;179490062;179490061 |
| N2B | 5764 | 17515;17516;17517 | chr2:178625336;178625335;178625334 | chr2:179490063;179490062;179490061 |
| Novex-1 | 5889 | 17890;17891;17892 | chr2:178625336;178625335;178625334 | chr2:179490063;179490062;179490061 |
| Novex-2 | 5956 | 18091;18092;18093 | chr2:178625336;178625335;178625334 | chr2:179490063;179490062;179490061 |
| 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/E | rs1559907952  |
-0.132 | 0.198 | D | 0.307 | 0.541 | 0.634385825132 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.1E-06 | 0 |
| D/E | rs1559907952 |
-0.132 | 0.198 | D | 0.307 | 0.541 | 0.634385825132 | gnomAD-4.0.0 | 6.88732E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02778E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.639 | likely_pathogenic | 0.6996 | pathogenic | -0.269 | Destabilizing | 0.978 | D | 0.738 | prob.delet. | D | 0.724031952 | None | None | N |
| D/C | 0.8985 | likely_pathogenic | 0.9246 | pathogenic | -0.139 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| D/E | 0.4379 | ambiguous | 0.4949 | ambiguous | -0.534 | Destabilizing | 0.198 | N | 0.307 | neutral | D | 0.615675091 | None | None | N |
| D/F | 0.8532 | likely_pathogenic | 0.8815 | pathogenic | 0.257 | Stabilizing | 0.999 | D | 0.832 | deleterious | None | None | None | None | N |
| D/G | 0.7548 | likely_pathogenic | 0.7867 | pathogenic | -0.617 | Destabilizing | 0.989 | D | 0.707 | prob.neutral | D | 0.759936362 | None | None | N |
| D/H | 0.5892 | likely_pathogenic | 0.6443 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | D | 0.70161744 | None | None | N |
| D/I | 0.8389 | likely_pathogenic | 0.8788 | pathogenic | 0.641 | Stabilizing | 0.999 | D | 0.825 | deleterious | None | None | None | None | N |
| D/K | 0.8977 | likely_pathogenic | 0.922 | pathogenic | -0.135 | Destabilizing | 0.983 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/L | 0.8366 | likely_pathogenic | 0.8778 | pathogenic | 0.641 | Stabilizing | 0.998 | D | 0.827 | deleterious | None | None | None | None | N |
| D/M | 0.855 | likely_pathogenic | 0.8848 | pathogenic | 0.887 | Stabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| D/N | 0.3469 | ambiguous | 0.3809 | ambiguous | -0.688 | Destabilizing | 0.989 | D | 0.639 | neutral | D | 0.762230974 | None | None | N |
| D/P | 0.9955 | likely_pathogenic | 0.9961 | pathogenic | 0.364 | Stabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| D/Q | 0.7558 | likely_pathogenic | 0.7926 | pathogenic | -0.506 | Destabilizing | 0.995 | D | 0.663 | neutral | None | None | None | None | N |
| D/R | 0.9384 | likely_pathogenic | 0.9469 | pathogenic | 0.08 | Stabilizing | 0.995 | D | 0.823 | deleterious | None | None | None | None | N |
| D/S | 0.5767 | likely_pathogenic | 0.6138 | pathogenic | -0.863 | Destabilizing | 0.983 | D | 0.583 | neutral | None | None | None | None | N |
| D/T | 0.7827 | likely_pathogenic | 0.8186 | pathogenic | -0.57 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | None | N |
| D/V | 0.6591 | likely_pathogenic | 0.7386 | pathogenic | 0.364 | Stabilizing | 0.997 | D | 0.827 | deleterious | D | 0.723294808 | None | None | N |
| D/W | 0.9652 | likely_pathogenic | 0.9705 | pathogenic | 0.441 | Stabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| D/Y | 0.3962 | ambiguous | 0.4727 | ambiguous | 0.5 | Stabilizing | 0.999 | D | 0.834 | deleterious | D | 0.723372694 | 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.