Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18233 | 54922;54923;54924 | chr2:178603990;178603989;178603988 | chr2:179468717;179468716;179468715 |
| N2AB | 16592 | 49999;50000;50001 | chr2:178603990;178603989;178603988 | chr2:179468717;179468716;179468715 |
| N2A | 15665 | 47218;47219;47220 | chr2:178603990;178603989;178603988 | chr2:179468717;179468716;179468715 |
| N2B | 9168 | 27727;27728;27729 | chr2:178603990;178603989;178603988 | chr2:179468717;179468716;179468715 |
| Novex-1 | 9293 | 28102;28103;28104 | chr2:178603990;178603989;178603988 | chr2:179468717;179468716;179468715 |
| Novex-2 | 9360 | 28303;28304;28305 | chr2:178603990;178603989;178603988 | chr2:179468717;179468716;179468715 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.999 | N | 0.611 | 0.453 | 0.562807121957 | gnomAD-4.0.0 | 1.5933E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86279E-06 | 0 | 0 |
| V/D | rs1060500469  |
None | 1.0 | N | 0.85 | 0.673 | 0.775735391153 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/D | rs1060500469 |
None | 1.0 | N | 0.85 | 0.673 | 0.775735391153 | gnomAD-4.0.0 | 6.5825E-06 | None | None | None | None | N | None | 2.41464E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs374996996 |
-0.132 | 0.997 | N | 0.508 | 0.298 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 1.29416E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7872 | likely_pathogenic | 0.6688 | pathogenic | -1.856 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.476682519 | None | None | N |
| V/C | 0.9245 | likely_pathogenic | 0.9222 | pathogenic | -1.459 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| V/D | 0.9919 | likely_pathogenic | 0.9893 | pathogenic | -2.564 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | N | 0.494457606 | None | None | N |
| V/E | 0.9785 | likely_pathogenic | 0.9711 | pathogenic | -2.294 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| V/F | 0.9236 | likely_pathogenic | 0.8579 | pathogenic | -1.1 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.490099058 | None | None | N |
| V/G | 0.9391 | likely_pathogenic | 0.9098 | pathogenic | -2.443 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.525995308 | None | None | N |
| V/H | 0.9942 | likely_pathogenic | 0.9904 | pathogenic | -2.342 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| V/I | 0.1439 | likely_benign | 0.1045 | benign | -0.2 | Destabilizing | 0.997 | D | 0.508 | neutral | N | 0.505688437 | None | None | N |
| V/K | 0.9877 | likely_pathogenic | 0.986 | pathogenic | -1.621 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/L | 0.78 | likely_pathogenic | 0.636 | pathogenic | -0.2 | Destabilizing | 0.997 | D | 0.624 | neutral | N | 0.489830763 | None | None | N |
| V/M | 0.854 | likely_pathogenic | 0.7079 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| V/N | 0.9778 | likely_pathogenic | 0.968 | pathogenic | -2.102 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| V/P | 0.9756 | likely_pathogenic | 0.9754 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| V/Q | 0.9788 | likely_pathogenic | 0.9665 | pathogenic | -1.831 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| V/R | 0.9789 | likely_pathogenic | 0.9748 | pathogenic | -1.659 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| V/S | 0.9304 | likely_pathogenic | 0.8666 | pathogenic | -2.71 | Highly Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| V/T | 0.8572 | likely_pathogenic | 0.7756 | pathogenic | -2.27 | Highly Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| V/W | 0.9988 | likely_pathogenic | 0.9972 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| V/Y | 0.9902 | likely_pathogenic | 0.9842 | pathogenic | -1.213 | Destabilizing | 1.0 | D | 0.82 | 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.