Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29880 | 89863;89864;89865 | chr2:178553262;178553261;178553260 | chr2:179417989;179417988;179417987 |
| N2AB | 28239 | 84940;84941;84942 | chr2:178553262;178553261;178553260 | chr2:179417989;179417988;179417987 |
| N2A | 27312 | 82159;82160;82161 | chr2:178553262;178553261;178553260 | chr2:179417989;179417988;179417987 |
| N2B | 20815 | 62668;62669;62670 | chr2:178553262;178553261;178553260 | chr2:179417989;179417988;179417987 |
| Novex-1 | 20940 | 63043;63044;63045 | chr2:178553262;178553261;178553260 | chr2:179417989;179417988;179417987 |
| Novex-2 | 21007 | 63244;63245;63246 | chr2:178553262;178553261;178553260 | chr2:179417989;179417988;179417987 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | 0.968 | N | 0.525 | 0.605 | 0.496628014799 | gnomAD-4.0.0 | 6.84934E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99452E-07 | 0 | 0 |
| L/R | rs781165041  |
-1.39 | 0.984 | D | 0.697 | 0.826 | 0.837555618272 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| L/R | rs781165041 |
-1.39 | 0.984 | D | 0.697 | 0.826 | 0.837555618272 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/R | rs781165041 |
-1.39 | 0.984 | D | 0.697 | 0.826 | 0.837555618272 | gnomAD-4.0.0 | 1.17841E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35614E-05 | 0 | 4.80384E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.5439 | ambiguous | 0.5089 | ambiguous | -2.621 | Highly Destabilizing | 0.919 | D | 0.541 | neutral | None | None | None | None | N |
| L/C | 0.7937 | likely_pathogenic | 0.7675 | pathogenic | -2.043 | Highly Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| L/D | 0.9787 | likely_pathogenic | 0.9737 | pathogenic | -2.998 | Highly Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/E | 0.9128 | likely_pathogenic | 0.9111 | pathogenic | -2.687 | Highly Destabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/F | 0.3414 | ambiguous | 0.3267 | benign | -1.578 | Destabilizing | 0.968 | D | 0.525 | neutral | N | 0.511974836 | None | None | N |
| L/G | 0.9118 | likely_pathogenic | 0.896 | pathogenic | -3.253 | Highly Destabilizing | 0.988 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/H | 0.8376 | likely_pathogenic | 0.82 | pathogenic | -2.867 | Highly Destabilizing | 0.999 | D | 0.723 | prob.delet. | D | 0.550843145 | None | None | N |
| L/I | 0.0848 | likely_benign | 0.0882 | benign | -0.75 | Destabilizing | 0.011 | N | 0.187 | neutral | N | 0.509204037 | None | None | N |
| L/K | 0.8825 | likely_pathogenic | 0.8869 | pathogenic | -2.004 | Highly Destabilizing | 0.988 | D | 0.659 | neutral | None | None | None | None | N |
| L/M | 0.1783 | likely_benign | 0.1778 | benign | -0.891 | Destabilizing | 0.307 | N | 0.359 | neutral | None | None | None | None | N |
| L/N | 0.9145 | likely_pathogenic | 0.9022 | pathogenic | -2.593 | Highly Destabilizing | 0.996 | D | 0.742 | deleterious | None | None | None | None | N |
| L/P | 0.6749 | likely_pathogenic | 0.634 | pathogenic | -1.359 | Destabilizing | 0.995 | D | 0.742 | deleterious | D | 0.539233351 | None | None | N |
| L/Q | 0.799 | likely_pathogenic | 0.7944 | pathogenic | -2.279 | Highly Destabilizing | 0.988 | D | 0.705 | prob.neutral | None | None | None | None | N |
| L/R | 0.8038 | likely_pathogenic | 0.8006 | pathogenic | -2.005 | Highly Destabilizing | 0.984 | D | 0.697 | prob.neutral | D | 0.545816716 | None | None | N |
| L/S | 0.8379 | likely_pathogenic | 0.8015 | pathogenic | -3.31 | Highly Destabilizing | 0.988 | D | 0.632 | neutral | None | None | None | None | N |
| L/T | 0.4869 | ambiguous | 0.4521 | ambiguous | -2.819 | Highly Destabilizing | 0.919 | D | 0.579 | neutral | None | None | None | None | N |
| L/V | 0.1239 | likely_benign | 0.1205 | benign | -1.359 | Destabilizing | 0.64 | D | 0.437 | neutral | D | 0.527560511 | None | None | N |
| L/W | 0.6987 | likely_pathogenic | 0.6619 | pathogenic | -1.969 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| L/Y | 0.8011 | likely_pathogenic | 0.782 | pathogenic | -1.684 | Destabilizing | 0.996 | D | 0.67 | 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.