Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22508 | 67747;67748;67749 | chr2:178579675;178579674;178579673 | chr2:179444402;179444401;179444400 |
| N2AB | 20867 | 62824;62825;62826 | chr2:178579675;178579674;178579673 | chr2:179444402;179444401;179444400 |
| N2A | 19940 | 60043;60044;60045 | chr2:178579675;178579674;178579673 | chr2:179444402;179444401;179444400 |
| N2B | 13443 | 40552;40553;40554 | chr2:178579675;178579674;178579673 | chr2:179444402;179444401;179444400 |
| Novex-1 | 13568 | 40927;40928;40929 | chr2:178579675;178579674;178579673 | chr2:179444402;179444401;179444400 |
| Novex-2 | 13635 | 41128;41129;41130 | chr2:178579675;178579674;178579673 | chr2:179444402;179444401;179444400 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/D | rs763377678  |
-3.301 | 0.81 | N | 0.717 | 0.453 | 0.600613607152 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/D | rs763377678 |
-3.301 | 0.81 | N | 0.717 | 0.453 | 0.600613607152 | gnomAD-4.0.0 | 3.18439E-06 | None | None | None | None | N | None | 0 | 4.57519E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/F | None | None | 0.004 | N | 0.155 | 0.211 | 0.332386209738 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| Y/N | None | -3.009 | 0.81 | N | 0.682 | 0.358 | None | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| Y/N | None | -3.009 | 0.81 | N | 0.682 | 0.358 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/N | None | -3.009 | 0.81 | N | 0.682 | 0.358 | None | gnomAD-4.0.0 | 6.57652E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47063E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6947 | likely_pathogenic | 0.7449 | pathogenic | -2.229 | Highly Destabilizing | 0.447 | N | 0.673 | neutral | None | None | None | None | N |
| Y/C | 0.2028 | likely_benign | 0.2402 | benign | -1.791 | Destabilizing | 0.99 | D | 0.653 | neutral | N | 0.486161313 | None | None | N |
| Y/D | 0.7507 | likely_pathogenic | 0.8412 | pathogenic | -1.535 | Destabilizing | 0.81 | D | 0.717 | prob.delet. | N | 0.51991524 | None | None | N |
| Y/E | 0.8909 | likely_pathogenic | 0.9301 | pathogenic | -1.358 | Destabilizing | 0.447 | N | 0.682 | prob.neutral | None | None | None | None | N |
| Y/F | 0.0921 | likely_benign | 0.0888 | benign | -0.773 | Destabilizing | 0.004 | N | 0.155 | neutral | N | 0.4864866 | None | None | N |
| Y/G | 0.6369 | likely_pathogenic | 0.6778 | pathogenic | -2.616 | Highly Destabilizing | 0.617 | D | 0.719 | prob.delet. | None | None | None | None | N |
| Y/H | 0.3091 | likely_benign | 0.382 | ambiguous | -1.265 | Destabilizing | 0.004 | N | 0.389 | neutral | N | 0.511750404 | None | None | N |
| Y/I | 0.5908 | likely_pathogenic | 0.6449 | pathogenic | -1.006 | Destabilizing | 0.739 | D | 0.683 | prob.neutral | None | None | None | None | N |
| Y/K | 0.86 | likely_pathogenic | 0.9066 | pathogenic | -1.878 | Destabilizing | 0.447 | N | 0.699 | prob.neutral | None | None | None | None | N |
| Y/L | 0.6061 | likely_pathogenic | 0.6639 | pathogenic | -1.006 | Destabilizing | 0.447 | N | 0.639 | neutral | None | None | None | None | N |
| Y/M | 0.7504 | likely_pathogenic | 0.7697 | pathogenic | -1.043 | Destabilizing | 0.92 | D | 0.619 | neutral | None | None | None | None | N |
| Y/N | 0.5002 | ambiguous | 0.6123 | pathogenic | -2.57 | Highly Destabilizing | 0.81 | D | 0.682 | prob.neutral | N | 0.501557496 | None | None | N |
| Y/P | 0.9771 | likely_pathogenic | 0.9861 | pathogenic | -1.417 | Destabilizing | 0.92 | D | 0.719 | prob.delet. | None | None | None | None | N |
| Y/Q | 0.7799 | likely_pathogenic | 0.8517 | pathogenic | -2.23 | Highly Destabilizing | 0.048 | N | 0.55 | neutral | None | None | None | None | N |
| Y/R | 0.7564 | likely_pathogenic | 0.8402 | pathogenic | -1.796 | Destabilizing | 0.739 | D | 0.672 | neutral | None | None | None | None | N |
| Y/S | 0.5283 | ambiguous | 0.6465 | pathogenic | -3.074 | Highly Destabilizing | 0.379 | N | 0.687 | prob.neutral | N | 0.496531066 | None | None | N |
| Y/T | 0.7161 | likely_pathogenic | 0.7823 | pathogenic | -2.772 | Highly Destabilizing | 0.85 | D | 0.691 | prob.neutral | None | None | None | None | N |
| Y/V | 0.5125 | ambiguous | 0.5672 | pathogenic | -1.417 | Destabilizing | 0.447 | N | 0.683 | prob.neutral | None | None | None | None | N |
| Y/W | 0.5365 | ambiguous | 0.5647 | pathogenic | -0.264 | Destabilizing | 0.992 | D | 0.613 | 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.