Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28969 | 87130;87131;87132 | chr2:178558554;178558553;178558552 | chr2:179423281;179423280;179423279 |
| N2AB | 27328 | 82207;82208;82209 | chr2:178558554;178558553;178558552 | chr2:179423281;179423280;179423279 |
| N2A | 26401 | 79426;79427;79428 | chr2:178558554;178558553;178558552 | chr2:179423281;179423280;179423279 |
| N2B | 19904 | 59935;59936;59937 | chr2:178558554;178558553;178558552 | chr2:179423281;179423280;179423279 |
| Novex-1 | 20029 | 60310;60311;60312 | chr2:178558554;178558553;178558552 | chr2:179423281;179423280;179423279 |
| Novex-2 | 20096 | 60511;60512;60513 | chr2:178558554;178558553;178558552 | chr2:179423281;179423280;179423279 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs139403831  |
-0.494 | 0.998 | N | 0.436 | 0.352 | 0.333154297509 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63441E-04 | None | 0 | 0 | 0 |
| D/E | rs139403831 |
-0.494 | 0.998 | N | 0.436 | 0.352 | 0.333154297509 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92827E-04 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| D/E | rs139403831 |
-0.494 | 0.998 | N | 0.436 | 0.352 | 0.333154297509 | gnomAD-4.0.0 | 1.23942E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.46389E-05 | None | 0 | 0 | 0 | 1.53714E-04 | 6.40471E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9276 | likely_pathogenic | 0.9106 | pathogenic | -0.184 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.487462031 | None | None | N |
| D/C | 0.9846 | likely_pathogenic | 0.9807 | pathogenic | 0.076 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/E | 0.9013 | likely_pathogenic | 0.9028 | pathogenic | -0.688 | Destabilizing | 0.998 | D | 0.436 | neutral | N | 0.487435578 | None | None | N |
| D/F | 0.9846 | likely_pathogenic | 0.985 | pathogenic | -0.447 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/G | 0.9018 | likely_pathogenic | 0.8815 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.505441382 | None | None | N |
| D/H | 0.9402 | likely_pathogenic | 0.9405 | pathogenic | -0.931 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.498755884 | None | None | N |
| D/I | 0.9787 | likely_pathogenic | 0.9765 | pathogenic | 0.518 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| D/K | 0.9805 | likely_pathogenic | 0.9816 | pathogenic | -0.176 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| D/L | 0.9624 | likely_pathogenic | 0.9619 | pathogenic | 0.518 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/M | 0.9892 | likely_pathogenic | 0.9878 | pathogenic | 0.984 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/N | 0.4063 | ambiguous | 0.3598 | ambiguous | -0.406 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.517654869 | None | None | N |
| D/P | 0.9867 | likely_pathogenic | 0.9844 | pathogenic | 0.31 | Stabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | N |
| D/Q | 0.9714 | likely_pathogenic | 0.9691 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/R | 0.9756 | likely_pathogenic | 0.977 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| D/S | 0.6649 | likely_pathogenic | 0.6006 | pathogenic | -0.581 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/T | 0.8413 | likely_pathogenic | 0.8163 | pathogenic | -0.361 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| D/V | 0.9475 | likely_pathogenic | 0.9439 | pathogenic | 0.31 | Stabilizing | 1.0 | D | 0.762 | deleterious | N | 0.496767648 | None | None | N |
| D/W | 0.9973 | likely_pathogenic | 0.9971 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/Y | 0.9133 | likely_pathogenic | 0.9068 | pathogenic | -0.278 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | D | 0.5375352879999999 | 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.