Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19134 | 57625;57626;57627 | chr2:178597682;178597681;178597680 | chr2:179462409;179462408;179462407 |
| N2AB | 17493 | 52702;52703;52704 | chr2:178597682;178597681;178597680 | chr2:179462409;179462408;179462407 |
| N2A | 16566 | 49921;49922;49923 | chr2:178597682;178597681;178597680 | chr2:179462409;179462408;179462407 |
| N2B | 10069 | 30430;30431;30432 | chr2:178597682;178597681;178597680 | chr2:179462409;179462408;179462407 |
| Novex-1 | 10194 | 30805;30806;30807 | chr2:178597682;178597681;178597680 | chr2:179462409;179462408;179462407 |
| Novex-2 | 10261 | 31006;31007;31008 | chr2:178597682;178597681;178597680 | chr2:179462409;179462408;179462407 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | None | None | 1.0 | N | 0.667 | 0.393 | 0.551135290849 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs1327049229  |
-0.627 | 1.0 | N | 0.72 | 0.358 | 0.423119698836 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs1327049229 |
-0.627 | 1.0 | N | 0.72 | 0.358 | 0.423119698836 | gnomAD-4.0.0 | 3.18434E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 3.02554E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.3548 | ambiguous | 0.4669 | ambiguous | -1.724 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.485146124 | None | None | N |
| P/C | 0.8739 | likely_pathogenic | 0.9215 | pathogenic | -0.856 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/D | 0.8476 | likely_pathogenic | 0.9046 | pathogenic | -1.88 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| P/E | 0.7596 | likely_pathogenic | 0.8506 | pathogenic | -1.851 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/F | 0.8986 | likely_pathogenic | 0.9548 | pathogenic | -1.383 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| P/G | 0.7121 | likely_pathogenic | 0.7949 | pathogenic | -2.066 | Highly Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| P/H | 0.6351 | likely_pathogenic | 0.7599 | pathogenic | -1.784 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.484540694 | None | None | N |
| P/I | 0.7954 | likely_pathogenic | 0.8913 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| P/K | 0.8156 | likely_pathogenic | 0.8913 | pathogenic | -1.506 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| P/L | 0.3975 | ambiguous | 0.5795 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.48717404 | None | None | N |
| P/M | 0.7728 | likely_pathogenic | 0.8704 | pathogenic | -0.508 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| P/N | 0.8039 | likely_pathogenic | 0.8774 | pathogenic | -1.222 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| P/Q | 0.629 | likely_pathogenic | 0.7659 | pathogenic | -1.351 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| P/R | 0.6928 | likely_pathogenic | 0.81 | pathogenic | -1.033 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.522127688 | None | None | N |
| P/S | 0.4555 | ambiguous | 0.5918 | pathogenic | -1.643 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.491786138 | None | None | N |
| P/T | 0.4225 | ambiguous | 0.5453 | ambiguous | -1.509 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.500117619 | None | None | N |
| P/V | 0.6523 | likely_pathogenic | 0.7822 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| P/W | 0.9378 | likely_pathogenic | 0.9725 | pathogenic | -1.664 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| P/Y | 0.8842 | likely_pathogenic | 0.946 | pathogenic | -1.382 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | 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.