Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16687 | 50284;50285;50286 | chr2:178612466;178612465;178612464 | chr2:179477193;179477192;179477191 |
| N2AB | 15046 | 45361;45362;45363 | chr2:178612466;178612465;178612464 | chr2:179477193;179477192;179477191 |
| N2A | 14119 | 42580;42581;42582 | chr2:178612466;178612465;178612464 | chr2:179477193;179477192;179477191 |
| N2B | 7622 | 23089;23090;23091 | chr2:178612466;178612465;178612464 | chr2:179477193;179477192;179477191 |
| Novex-1 | 7747 | 23464;23465;23466 | chr2:178612466;178612465;178612464 | chr2:179477193;179477192;179477191 |
| Novex-2 | 7814 | 23665;23666;23667 | chr2:178612466;178612465;178612464 | chr2:179477193;179477192;179477191 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1559789920  |
None | 0.97 | D | 0.679 | 0.42 | 0.163833314356 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.67E-05 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs1559789920 |
None | 0.97 | D | 0.679 | 0.42 | 0.163833314356 | gnomAD-4.0.0 | 1.59425E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79298E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs727504194 |
-1.662 | 0.025 | N | 0.299 | 0.058 | 0.447311733946 | gnomAD-2.1.1 | 7.33E-05 | None | None | None | None | N | None | 0 | 4.95165E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.67898E-04 |
| I/V | rs727504194 |
-1.662 | 0.025 | N | 0.299 | 0.058 | 0.447311733946 | gnomAD-3.1.2 | 1.31636E-04 | None | None | None | None | N | None | 0 | 1.31113E-03 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs727504194 |
-1.662 | 0.025 | N | 0.299 | 0.058 | 0.447311733946 | gnomAD-4.0.0 | 2.72912E-05 | None | None | None | None | N | None | 0 | 7.18007E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60344E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.809 | likely_pathogenic | 0.8691 | pathogenic | -2.861 | Highly Destabilizing | 0.86 | D | 0.625 | neutral | None | None | None | None | N |
| I/C | 0.937 | likely_pathogenic | 0.9478 | pathogenic | -2.256 | Highly Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/D | 0.9898 | likely_pathogenic | 0.9946 | pathogenic | -3.508 | Highly Destabilizing | 0.993 | D | 0.747 | deleterious | None | None | None | None | N |
| I/E | 0.9593 | likely_pathogenic | 0.9772 | pathogenic | -3.323 | Highly Destabilizing | 0.993 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/F | 0.5174 | ambiguous | 0.5917 | pathogenic | -1.683 | Destabilizing | 0.032 | N | 0.467 | neutral | N | 0.493481465 | None | None | N |
| I/G | 0.9801 | likely_pathogenic | 0.9886 | pathogenic | -3.334 | Highly Destabilizing | 0.978 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/H | 0.9017 | likely_pathogenic | 0.9374 | pathogenic | -2.634 | Highly Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| I/K | 0.8114 | likely_pathogenic | 0.9071 | pathogenic | -2.216 | Highly Destabilizing | 0.978 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/L | 0.3142 | likely_benign | 0.3412 | ambiguous | -1.489 | Destabilizing | 0.294 | N | 0.465 | neutral | N | 0.470159179 | None | None | N |
| I/M | 0.3203 | likely_benign | 0.3748 | ambiguous | -1.514 | Destabilizing | 0.97 | D | 0.679 | prob.neutral | D | 0.558474943 | None | None | N |
| I/N | 0.8831 | likely_pathogenic | 0.9246 | pathogenic | -2.55 | Highly Destabilizing | 0.99 | D | 0.763 | deleterious | N | 0.495027421 | None | None | N |
| I/P | 0.9975 | likely_pathogenic | 0.9985 | pathogenic | -1.931 | Destabilizing | 0.993 | D | 0.761 | deleterious | None | None | None | None | N |
| I/Q | 0.8997 | likely_pathogenic | 0.9367 | pathogenic | -2.483 | Highly Destabilizing | 0.993 | D | 0.759 | deleterious | None | None | None | None | N |
| I/R | 0.7341 | likely_pathogenic | 0.8524 | pathogenic | -1.762 | Destabilizing | 0.978 | D | 0.763 | deleterious | None | None | None | None | N |
| I/S | 0.8395 | likely_pathogenic | 0.8953 | pathogenic | -3.147 | Highly Destabilizing | 0.97 | D | 0.69 | prob.neutral | N | 0.45849504 | None | None | N |
| I/T | 0.4955 | ambiguous | 0.6099 | pathogenic | -2.842 | Highly Destabilizing | 0.822 | D | 0.668 | neutral | N | 0.476705774 | None | None | N |
| I/V | 0.0956 | likely_benign | 0.1047 | benign | -1.931 | Destabilizing | 0.025 | N | 0.299 | neutral | N | 0.443468178 | None | None | N |
| I/W | 0.9663 | likely_pathogenic | 0.9746 | pathogenic | -2.069 | Highly Destabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| I/Y | 0.8985 | likely_pathogenic | 0.9242 | pathogenic | -1.9 | Destabilizing | 0.915 | D | 0.707 | 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.