Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21757 | 65494;65495;65496 | chr2:178584282;178584281;178584280 | chr2:179449009;179449008;179449007 |
| N2AB | 20116 | 60571;60572;60573 | chr2:178584282;178584281;178584280 | chr2:179449009;179449008;179449007 |
| N2A | 19189 | 57790;57791;57792 | chr2:178584282;178584281;178584280 | chr2:179449009;179449008;179449007 |
| N2B | 12692 | 38299;38300;38301 | chr2:178584282;178584281;178584280 | chr2:179449009;179449008;179449007 |
| Novex-1 | 12817 | 38674;38675;38676 | chr2:178584282;178584281;178584280 | chr2:179449009;179449008;179449007 |
| Novex-2 | 12884 | 38875;38876;38877 | chr2:178584282;178584281;178584280 | chr2:179449009;179449008;179449007 |
| 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/S | rs1166497792  |
None | 0.983 | N | 0.655 | 0.42 | 0.432154444652 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs1166497792 |
None | 0.983 | N | 0.655 | 0.42 | 0.432154444652 | gnomAD-4.0.0 | 1.53155E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.83864E-05 | 0 | 0 |
| P/T | rs1166497792 |
None | 0.997 | N | 0.595 | 0.423 | 0.503806528429 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs1166497792 |
None | 0.997 | N | 0.595 | 0.423 | 0.503806528429 | gnomAD-4.0.0 | 4.17695E-06 | None | None | None | None | I | None | 3.53182E-05 | 0 | None | 0 | 2.47427E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1425 | likely_benign | 0.1116 | benign | -0.219 | Destabilizing | 0.603 | D | 0.293 | neutral | N | 0.518832966 | None | None | I |
| P/C | 0.8092 | likely_pathogenic | 0.7212 | pathogenic | -0.652 | Destabilizing | 1.0 | D | 0.737 | deleterious | None | None | None | None | I |
| P/D | 0.7963 | likely_pathogenic | 0.7225 | pathogenic | -0.313 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | I |
| P/E | 0.6144 | likely_pathogenic | 0.5081 | ambiguous | -0.436 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | I |
| P/F | 0.8393 | likely_pathogenic | 0.7668 | pathogenic | -0.653 | Destabilizing | 1.0 | D | 0.707 | prob.delet. | None | None | None | None | I |
| P/G | 0.6176 | likely_pathogenic | 0.5571 | ambiguous | -0.273 | Destabilizing | 0.993 | D | 0.582 | neutral | None | None | None | None | I |
| P/H | 0.5608 | ambiguous | 0.4527 | ambiguous | 0.064 | Stabilizing | 1.0 | D | 0.687 | prob.delet. | None | None | None | None | I |
| P/I | 0.6415 | likely_pathogenic | 0.5331 | ambiguous | -0.221 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| P/K | 0.7005 | likely_pathogenic | 0.5809 | pathogenic | -0.272 | Destabilizing | 0.999 | D | 0.6 | neutral | None | None | None | None | I |
| P/L | 0.2874 | likely_benign | 0.2176 | benign | -0.221 | Destabilizing | 0.997 | D | 0.609 | neutral | N | 0.491235737 | None | None | I |
| P/M | 0.5832 | likely_pathogenic | 0.4779 | ambiguous | -0.46 | Destabilizing | 1.0 | D | 0.669 | prob.neutral | None | None | None | None | I |
| P/N | 0.6938 | likely_pathogenic | 0.6089 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.701 | prob.delet. | None | None | None | None | I |
| P/Q | 0.3985 | ambiguous | 0.3001 | benign | -0.242 | Destabilizing | 1.0 | D | 0.567 | neutral | N | 0.489879384 | None | None | I |
| P/R | 0.5065 | ambiguous | 0.3965 | ambiguous | 0.163 | Stabilizing | 0.999 | D | 0.657 | prob.neutral | N | 0.501996158 | None | None | I |
| P/S | 0.3679 | ambiguous | 0.2882 | benign | -0.305 | Destabilizing | 0.983 | D | 0.655 | prob.neutral | N | 0.501742669 | None | None | I |
| P/T | 0.3041 | likely_benign | 0.2266 | benign | -0.34 | Destabilizing | 0.997 | D | 0.595 | neutral | N | 0.519846924 | None | None | I |
| P/V | 0.4182 | ambiguous | 0.3316 | benign | -0.192 | Destabilizing | 0.998 | D | 0.53 | neutral | None | None | None | None | I |
| P/W | 0.9176 | likely_pathogenic | 0.8757 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.73 | deleterious | None | None | None | None | I |
| P/Y | 0.8268 | likely_pathogenic | 0.7424 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | 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.