Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16403 | 49432;49433;49434 | chr2:178614190;178614189;178614188 | chr2:179478917;179478916;179478915 |
| N2AB | 14762 | 44509;44510;44511 | chr2:178614190;178614189;178614188 | chr2:179478917;179478916;179478915 |
| N2A | 13835 | 41728;41729;41730 | chr2:178614190;178614189;178614188 | chr2:179478917;179478916;179478915 |
| N2B | 7338 | 22237;22238;22239 | chr2:178614190;178614189;178614188 | chr2:179478917;179478916;179478915 |
| Novex-1 | 7463 | 22612;22613;22614 | chr2:178614190;178614189;178614188 | chr2:179478917;179478916;179478915 |
| Novex-2 | 7530 | 22813;22814;22815 | chr2:178614190;178614189;178614188 | chr2:179478917;179478916;179478915 |
| 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/P | rs746009199  |
-0.249 | 1.0 | N | 0.777 | 0.458 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs746009199 |
-0.249 | 1.0 | N | 0.777 | 0.458 | None | gnomAD-3.1.2 | 2.64E-05 | None | None | None | None | N | None | 9.67E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs746009199 |
-0.249 | 1.0 | N | 0.777 | 0.458 | None | gnomAD-4.0.0 | 6.4169E-06 | None | None | None | None | N | None | 8.47716E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs746009199 |
0.049 | 0.999 | N | 0.433 | 0.262 | 0.263612267334 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| S/Y | rs774691242 |
-0.651 | 1.0 | N | 0.804 | 0.445 | 0.554841954621 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 1.41004E-04 |
| S/Y | rs774691242 |
-0.651 | 1.0 | N | 0.804 | 0.445 | 0.554841954621 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/Y | rs774691242 |
-0.651 | 1.0 | N | 0.804 | 0.445 | 0.554841954621 | gnomAD-4.0.0 | 6.41682E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.57045E-05 | 0 | 9.58529E-06 | 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 | 0.0846 | likely_benign | 0.0778 | benign | -0.51 | Destabilizing | 0.997 | D | 0.389 | neutral | N | 0.457904476 | None | None | N |
| S/C | 0.2209 | likely_benign | 0.182 | benign | -0.299 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.633353025 | None | None | N |
| S/D | 0.837 | likely_pathogenic | 0.7204 | pathogenic | -0.132 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | N |
| S/E | 0.8719 | likely_pathogenic | 0.789 | pathogenic | -0.214 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| S/F | 0.5451 | ambiguous | 0.4073 | ambiguous | -1.031 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.481517603 | None | None | N |
| S/G | 0.1497 | likely_benign | 0.121 | benign | -0.647 | Destabilizing | 0.999 | D | 0.464 | neutral | None | None | None | None | N |
| S/H | 0.7545 | likely_pathogenic | 0.6562 | pathogenic | -1.225 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| S/I | 0.5021 | ambiguous | 0.4037 | ambiguous | -0.272 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| S/K | 0.9543 | likely_pathogenic | 0.9202 | pathogenic | -0.565 | Destabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | N |
| S/L | 0.2194 | likely_benign | 0.1703 | benign | -0.272 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/M | 0.4034 | ambiguous | 0.3206 | benign | 0.164 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| S/N | 0.4324 | ambiguous | 0.3116 | benign | -0.308 | Destabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| S/P | 0.4658 | ambiguous | 0.3957 | ambiguous | -0.322 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.481695777 | None | None | N |
| S/Q | 0.8214 | likely_pathogenic | 0.7445 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| S/R | 0.9359 | likely_pathogenic | 0.8985 | pathogenic | -0.338 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| S/T | 0.1654 | likely_benign | 0.1371 | benign | -0.413 | Destabilizing | 0.999 | D | 0.433 | neutral | N | 0.440478475 | None | None | N |
| S/V | 0.3979 | ambiguous | 0.3254 | benign | -0.322 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| S/W | 0.7412 | likely_pathogenic | 0.6468 | pathogenic | -0.988 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| S/Y | 0.5218 | ambiguous | 0.4019 | ambiguous | -0.727 | Destabilizing | 1.0 | D | 0.804 | deleterious | N | 0.472927298 | 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.