Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25248 | 75967;75968;75969 | chr2:178570390;178570389;178570388 | chr2:179435117;179435116;179435115 |
| N2AB | 23607 | 71044;71045;71046 | chr2:178570390;178570389;178570388 | chr2:179435117;179435116;179435115 |
| N2A | 22680 | 68263;68264;68265 | chr2:178570390;178570389;178570388 | chr2:179435117;179435116;179435115 |
| N2B | 16183 | 48772;48773;48774 | chr2:178570390;178570389;178570388 | chr2:179435117;179435116;179435115 |
| Novex-1 | 16308 | 49147;49148;49149 | chr2:178570390;178570389;178570388 | chr2:179435117;179435116;179435115 |
| Novex-2 | 16375 | 49348;49349;49350 | chr2:178570390;178570389;178570388 | chr2:179435117;179435116;179435115 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.892 | N | 0.337 | 0.204 | 0.222439326576 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| S/N | rs1192508710  |
-0.092 | 0.892 | N | 0.361 | 0.207 | 0.229264304666 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| S/N | rs1192508710 |
-0.092 | 0.892 | N | 0.361 | 0.207 | 0.229264304666 | 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 |
| S/N | rs1192508710 |
-0.092 | 0.892 | N | 0.361 | 0.207 | 0.229264304666 | gnomAD-4.0.0 | 6.57566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47111E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.3302 | likely_benign | 0.322 | benign | -0.274 | Destabilizing | 0.693 | D | 0.393 | neutral | None | None | None | None | N |
| S/C | 0.5658 | likely_pathogenic | 0.5907 | pathogenic | -0.33 | Destabilizing | 0.999 | D | 0.539 | neutral | N | 0.503755861 | None | None | N |
| S/D | 0.9347 | likely_pathogenic | 0.9403 | pathogenic | 0.092 | Stabilizing | 0.916 | D | 0.337 | neutral | None | None | None | None | N |
| S/E | 0.9636 | likely_pathogenic | 0.963 | pathogenic | -0.007 | Destabilizing | 0.845 | D | 0.334 | neutral | None | None | None | None | N |
| S/F | 0.903 | likely_pathogenic | 0.9057 | pathogenic | -0.857 | Destabilizing | 0.996 | D | 0.598 | neutral | None | None | None | None | N |
| S/G | 0.3715 | ambiguous | 0.3616 | ambiguous | -0.375 | Destabilizing | 0.892 | D | 0.337 | neutral | N | 0.446789275 | None | None | N |
| S/H | 0.8791 | likely_pathogenic | 0.8884 | pathogenic | -0.794 | Destabilizing | 0.997 | D | 0.496 | neutral | None | None | None | None | N |
| S/I | 0.8974 | likely_pathogenic | 0.8974 | pathogenic | -0.141 | Destabilizing | 0.983 | D | 0.596 | neutral | N | 0.49510858 | None | None | N |
| S/K | 0.9842 | likely_pathogenic | 0.9816 | pathogenic | -0.521 | Destabilizing | 0.033 | N | 0.256 | neutral | None | None | None | None | N |
| S/L | 0.6089 | likely_pathogenic | 0.6168 | pathogenic | -0.141 | Destabilizing | 0.916 | D | 0.473 | neutral | None | None | None | None | N |
| S/M | 0.7925 | likely_pathogenic | 0.7981 | pathogenic | -0.016 | Destabilizing | 0.999 | D | 0.501 | neutral | None | None | None | None | N |
| S/N | 0.7245 | likely_pathogenic | 0.7434 | pathogenic | -0.226 | Destabilizing | 0.892 | D | 0.361 | neutral | N | 0.498410174 | None | None | N |
| S/P | 0.8996 | likely_pathogenic | 0.9178 | pathogenic | -0.157 | Destabilizing | 0.987 | D | 0.493 | neutral | None | None | None | None | N |
| S/Q | 0.932 | likely_pathogenic | 0.9284 | pathogenic | -0.475 | Destabilizing | 0.975 | D | 0.417 | neutral | None | None | None | None | N |
| S/R | 0.9742 | likely_pathogenic | 0.9691 | pathogenic | -0.268 | Destabilizing | 0.935 | D | 0.421 | neutral | N | 0.471190974 | None | None | N |
| S/T | 0.329 | likely_benign | 0.327 | benign | -0.337 | Destabilizing | 0.892 | D | 0.351 | neutral | N | 0.51959631 | None | None | N |
| S/V | 0.8227 | likely_pathogenic | 0.8318 | pathogenic | -0.157 | Destabilizing | 0.975 | D | 0.516 | neutral | None | None | None | None | N |
| S/W | 0.9049 | likely_pathogenic | 0.9113 | pathogenic | -0.887 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| S/Y | 0.8637 | likely_pathogenic | 0.8643 | pathogenic | -0.603 | Destabilizing | 0.996 | D | 0.601 | 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.