Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33747 | 101464;101465;101466 | chr2:178535376;178535375;178535374 | chr2:179400103;179400102;179400101 |
| N2AB | 32106 | 96541;96542;96543 | chr2:178535376;178535375;178535374 | chr2:179400103;179400102;179400101 |
| N2A | 31179 | 93760;93761;93762 | chr2:178535376;178535375;178535374 | chr2:179400103;179400102;179400101 |
| N2B | 24682 | 74269;74270;74271 | chr2:178535376;178535375;178535374 | chr2:179400103;179400102;179400101 |
| Novex-1 | 24807 | 74644;74645;74646 | chr2:178535376;178535375;178535374 | chr2:179400103;179400102;179400101 |
| Novex-2 | 24874 | 74845;74846;74847 | chr2:178535376;178535375;178535374 | chr2:179400103;179400102;179400101 |
| 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/C | None | None | 1.0 | N | 0.672 | 0.447 | 0.55025283692 | 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/H | rs1310463317  |
-1.088 | 0.998 | D | 0.505 | 0.466 | 0.387529464389 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/H | rs1310463317 |
-1.088 | 0.998 | D | 0.505 | 0.466 | 0.387529464389 | gnomAD-4.0.0 | 1.59108E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 | 0.9368 | likely_pathogenic | 0.947 | pathogenic | -2.273 | Highly Destabilizing | 0.995 | D | 0.547 | neutral | None | None | None | None | N |
| Y/C | 0.3766 | ambiguous | 0.4381 | ambiguous | -1.224 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.495319514 | None | None | N |
| Y/D | 0.9676 | likely_pathogenic | 0.9758 | pathogenic | -1.236 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.505761005 | None | None | N |
| Y/E | 0.9862 | likely_pathogenic | 0.9877 | pathogenic | -1.086 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| Y/F | 0.1618 | likely_benign | 0.1644 | benign | -0.648 | Destabilizing | 0.898 | D | 0.424 | neutral | N | 0.485678524 | None | None | N |
| Y/G | 0.9151 | likely_pathogenic | 0.934 | pathogenic | -2.647 | Highly Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| Y/H | 0.6811 | likely_pathogenic | 0.744 | pathogenic | -1.063 | Destabilizing | 0.998 | D | 0.505 | neutral | D | 0.523602194 | None | None | N |
| Y/I | 0.8764 | likely_pathogenic | 0.8898 | pathogenic | -1.104 | Destabilizing | 0.049 | N | 0.268 | neutral | None | None | None | None | N |
| Y/K | 0.9764 | likely_pathogenic | 0.9802 | pathogenic | -1.449 | Destabilizing | 0.996 | D | 0.624 | neutral | None | None | None | None | N |
| Y/L | 0.7531 | likely_pathogenic | 0.7826 | pathogenic | -1.104 | Destabilizing | 0.012 | N | 0.269 | neutral | None | None | None | None | N |
| Y/M | 0.8592 | likely_pathogenic | 0.8743 | pathogenic | -0.911 | Destabilizing | 0.99 | D | 0.617 | neutral | None | None | None | None | N |
| Y/N | 0.8358 | likely_pathogenic | 0.8784 | pathogenic | -1.98 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.512090881 | None | None | N |
| Y/P | 0.9974 | likely_pathogenic | 0.9983 | pathogenic | -1.494 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| Y/Q | 0.9574 | likely_pathogenic | 0.9652 | pathogenic | -1.767 | Destabilizing | 0.998 | D | 0.609 | neutral | None | None | None | None | N |
| Y/R | 0.9501 | likely_pathogenic | 0.9585 | pathogenic | -1.187 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| Y/S | 0.8611 | likely_pathogenic | 0.895 | pathogenic | -2.515 | Highly Destabilizing | 0.999 | D | 0.595 | neutral | N | 0.479908069 | None | None | N |
| Y/T | 0.942 | likely_pathogenic | 0.9572 | pathogenic | -2.257 | Highly Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | N |
| Y/V | 0.8073 | likely_pathogenic | 0.8327 | pathogenic | -1.494 | Destabilizing | 0.953 | D | 0.459 | neutral | None | None | None | None | N |
| Y/W | 0.7411 | likely_pathogenic | 0.774 | pathogenic | -0.117 | Destabilizing | 1.0 | D | 0.511 | 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.