Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31121 | 93586;93587;93588 | chr2:178548265;178548264;178548263 | chr2:179412992;179412991;179412990 |
| N2AB | 29480 | 88663;88664;88665 | chr2:178548265;178548264;178548263 | chr2:179412992;179412991;179412990 |
| N2A | 28553 | 85882;85883;85884 | chr2:178548265;178548264;178548263 | chr2:179412992;179412991;179412990 |
| N2B | 22056 | 66391;66392;66393 | chr2:178548265;178548264;178548263 | chr2:179412992;179412991;179412990 |
| Novex-1 | 22181 | 66766;66767;66768 | chr2:178548265;178548264;178548263 | chr2:179412992;179412991;179412990 |
| Novex-2 | 22248 | 66967;66968;66969 | chr2:178548265;178548264;178548263 | chr2:179412992;179412991;179412990 |
| 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/H | rs1387694894  |
0.634 | 1.0 | N | 0.845 | 0.406 | 0.317958651998 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/H | rs1387694894 |
0.634 | 1.0 | N | 0.845 | 0.406 | 0.317958651998 | gnomAD-4.0.0 | 1.59109E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-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 | 0.6137 | likely_pathogenic | 0.4921 | ambiguous | -0.438 | Destabilizing | 1.0 | D | 0.833 | deleterious | N | 0.43594035 | None | None | I |
| D/C | 0.9476 | likely_pathogenic | 0.9178 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | I |
| D/E | 0.5109 | ambiguous | 0.4069 | ambiguous | -0.64 | Destabilizing | 1.0 | D | 0.469 | neutral | N | 0.396728601 | None | None | I |
| D/F | 0.9092 | likely_pathogenic | 0.8634 | pathogenic | -0.11 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| D/G | 0.6676 | likely_pathogenic | 0.5686 | pathogenic | -0.761 | Destabilizing | 1.0 | D | 0.839 | deleterious | N | 0.423357842 | None | None | I |
| D/H | 0.7743 | likely_pathogenic | 0.6511 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.845 | deleterious | N | 0.436420353 | None | None | I |
| D/I | 0.8145 | likely_pathogenic | 0.7257 | pathogenic | 0.402 | Stabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | I |
| D/K | 0.9099 | likely_pathogenic | 0.8363 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| D/L | 0.8016 | likely_pathogenic | 0.7209 | pathogenic | 0.402 | Stabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | I |
| D/M | 0.9182 | likely_pathogenic | 0.8778 | pathogenic | 0.684 | Stabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| D/N | 0.4189 | ambiguous | 0.3457 | ambiguous | -0.649 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.430553173 | None | None | I |
| D/P | 0.9902 | likely_pathogenic | 0.9817 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | I |
| D/Q | 0.82 | likely_pathogenic | 0.7277 | pathogenic | -0.53 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| D/R | 0.8942 | likely_pathogenic | 0.8153 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| D/S | 0.48 | ambiguous | 0.3822 | ambiguous | -0.836 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/T | 0.6929 | likely_pathogenic | 0.5833 | pathogenic | -0.579 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | I |
| D/V | 0.6371 | likely_pathogenic | 0.5108 | ambiguous | 0.147 | Stabilizing | 1.0 | D | 0.893 | deleterious | N | 0.412063413 | None | None | I |
| D/W | 0.9796 | likely_pathogenic | 0.967 | pathogenic | 0.049 | Stabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| D/Y | 0.6653 | likely_pathogenic | 0.5325 | ambiguous | 0.125 | Stabilizing | 1.0 | D | 0.887 | deleterious | N | 0.482867505 | 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.