Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3064 | 9415;9416;9417 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
| N2AB | 3064 | 9415;9416;9417 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
| N2A | 3064 | 9415;9416;9417 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
| N2B | 3018 | 9277;9278;9279 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
| Novex-1 | 3018 | 9277;9278;9279 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
| Novex-2 | 3018 | 9277;9278;9279 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
| Novex-3 | 3064 | 9415;9416;9417 | chr2:178768129;178768128;178768127 | chr2:179632856;179632855;179632854 |
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/T | rs769120910  |
-2.192 | 1.0 | D | 0.694 | 0.642 | 0.774620572007 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/T | rs769120910 |
-2.192 | 1.0 | D | 0.694 | 0.642 | 0.774620572007 | gnomAD-4.0.0 | 3.18136E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77731E-05 | None | 0 | 0 | 2.85656E-06 | 0 | 0 |
| I/V | None | None | 0.993 | N | 0.309 | 0.322 | 0.646692631277 | gnomAD-4.0.0 | 1.59066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85654E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9388 | likely_pathogenic | 0.9408 | pathogenic | -2.334 | Highly Destabilizing | 0.999 | D | 0.517 | neutral | None | None | None | None | N |
| I/C | 0.976 | likely_pathogenic | 0.9743 | pathogenic | -1.541 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| I/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -2.451 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| I/E | 0.9975 | likely_pathogenic | 0.9966 | pathogenic | -2.218 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| I/F | 0.8841 | likely_pathogenic | 0.826 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.653 | neutral | D | 0.542211438 | None | None | N |
| I/G | 0.994 | likely_pathogenic | 0.9928 | pathogenic | -2.89 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| I/H | 0.998 | likely_pathogenic | 0.9965 | pathogenic | -2.36 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| I/K | 0.9949 | likely_pathogenic | 0.9922 | pathogenic | -1.608 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| I/L | 0.1875 | likely_benign | 0.1467 | benign | -0.727 | Destabilizing | 0.993 | D | 0.359 | neutral | N | 0.423965343 | None | None | N |
| I/M | 0.3388 | likely_benign | 0.2833 | benign | -0.704 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.511072729 | None | None | N |
| I/N | 0.9889 | likely_pathogenic | 0.9845 | pathogenic | -1.938 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.624407966 | None | None | N |
| I/P | 0.9599 | likely_pathogenic | 0.9499 | pathogenic | -1.243 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| I/Q | 0.9939 | likely_pathogenic | 0.9907 | pathogenic | -1.781 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| I/R | 0.993 | likely_pathogenic | 0.9888 | pathogenic | -1.42 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| I/S | 0.9785 | likely_pathogenic | 0.9733 | pathogenic | -2.666 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.657035028 | None | None | N |
| I/T | 0.9574 | likely_pathogenic | 0.9598 | pathogenic | -2.283 | Highly Destabilizing | 1.0 | D | 0.694 | prob.neutral | D | 0.622928781 | None | None | N |
| I/V | 0.2316 | likely_benign | 0.2389 | benign | -1.243 | Destabilizing | 0.993 | D | 0.309 | neutral | N | 0.502334069 | None | None | N |
| I/W | 0.9979 | likely_pathogenic | 0.996 | pathogenic | -1.718 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| I/Y | 0.9949 | likely_pathogenic | 0.9908 | pathogenic | -1.402 | Destabilizing | 1.0 | D | 0.785 | deleterious | 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.