Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32917 | 98974;98975;98976 | chr2:178539186;178539185;178539184 | chr2:179403913;179403912;179403911 |
| N2AB | 31276 | 94051;94052;94053 | chr2:178539186;178539185;178539184 | chr2:179403913;179403912;179403911 |
| N2A | 30349 | 91270;91271;91272 | chr2:178539186;178539185;178539184 | chr2:179403913;179403912;179403911 |
| N2B | 23852 | 71779;71780;71781 | chr2:178539186;178539185;178539184 | chr2:179403913;179403912;179403911 |
| Novex-1 | 23977 | 72154;72155;72156 | chr2:178539186;178539185;178539184 | chr2:179403913;179403912;179403911 |
| Novex-2 | 24044 | 72355;72356;72357 | chr2:178539186;178539185;178539184 | chr2:179403913;179403912;179403911 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs561932256  |
-0.464 | 0.999 | N | 0.773 | 0.384 | None | gnomAD-2.1.1 | 2.81E-05 | None | None | None | None | N | None | 1.93748E-04 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 1.65508E-04 |
| S/F | rs561932256 |
-0.464 | 0.999 | N | 0.773 | 0.384 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.44844E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs561932256 |
-0.464 | 0.999 | N | 0.773 | 0.384 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/F | rs561932256 |
-0.464 | 0.999 | N | 0.773 | 0.384 | None | gnomAD-4.0.0 | 1.73505E-05 | None | None | None | None | N | None | 1.86637E-04 | 3.33311E-05 | None | 0 | 0 | None | 0 | 0 | 5.9334E-06 | 1.09798E-05 | 6.40225E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1096 | likely_benign | 0.1066 | benign | -0.666 | Destabilizing | 0.973 | D | 0.393 | neutral | N | 0.486124028 | None | None | N |
| S/C | 0.1294 | likely_benign | 0.1367 | benign | -0.3 | Destabilizing | 0.391 | N | 0.425 | neutral | N | 0.487798562 | None | None | N |
| S/D | 0.9146 | likely_pathogenic | 0.9254 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | N |
| S/E | 0.8863 | likely_pathogenic | 0.9022 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| S/F | 0.2867 | likely_benign | 0.3524 | ambiguous | -0.477 | Destabilizing | 0.999 | D | 0.773 | deleterious | N | 0.507459753 | None | None | N |
| S/G | 0.2527 | likely_benign | 0.2294 | benign | -1.045 | Destabilizing | 0.996 | D | 0.441 | neutral | None | None | None | None | N |
| S/H | 0.5748 | likely_pathogenic | 0.6252 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| S/I | 0.364 | ambiguous | 0.3745 | ambiguous | 0.276 | Stabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| S/K | 0.9424 | likely_pathogenic | 0.9485 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.577 | neutral | None | None | None | None | N |
| S/L | 0.1679 | likely_benign | 0.182 | benign | 0.276 | Stabilizing | 0.992 | D | 0.593 | neutral | None | None | None | None | N |
| S/M | 0.2861 | likely_benign | 0.283 | benign | 0.271 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| S/N | 0.429 | ambiguous | 0.4564 | ambiguous | -0.647 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | N |
| S/P | 0.9784 | likely_pathogenic | 0.9863 | pathogenic | -0.002 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | D | 0.525399423 | None | None | N |
| S/Q | 0.7172 | likely_pathogenic | 0.7288 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| S/R | 0.8977 | likely_pathogenic | 0.9073 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| S/T | 0.1524 | likely_benign | 0.1553 | benign | -0.474 | Destabilizing | 0.994 | D | 0.449 | neutral | N | 0.467863554 | None | None | N |
| S/V | 0.3311 | likely_benign | 0.342 | ambiguous | -0.002 | Destabilizing | 0.998 | D | 0.646 | neutral | None | None | None | None | N |
| S/W | 0.5765 | likely_pathogenic | 0.6525 | pathogenic | -0.634 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| S/Y | 0.3133 | likely_benign | 0.3857 | ambiguous | -0.241 | Destabilizing | 0.999 | D | 0.774 | deleterious | N | 0.514043118 | 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.