Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32842 | 98749;98750;98751 | chr2:178539541;178539540;178539539 | chr2:179404268;179404267;179404266 |
| N2AB | 31201 | 93826;93827;93828 | chr2:178539541;178539540;178539539 | chr2:179404268;179404267;179404266 |
| N2A | 30274 | 91045;91046;91047 | chr2:178539541;178539540;178539539 | chr2:179404268;179404267;179404266 |
| N2B | 23777 | 71554;71555;71556 | chr2:178539541;178539540;178539539 | chr2:179404268;179404267;179404266 |
| Novex-1 | 23902 | 71929;71930;71931 | chr2:178539541;178539540;178539539 | chr2:179404268;179404267;179404266 |
| Novex-2 | 23969 | 72130;72131;72132 | chr2:178539541;178539540;178539539 | chr2:179404268;179404267;179404266 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs199647622  |
-0.475 | 1.0 | N | 0.554 | 0.297 | 0.336155897331 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| A/S | rs199647622 |
-0.475 | 1.0 | N | 0.554 | 0.297 | 0.336155897331 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/S | rs199647622 |
-0.475 | 1.0 | N | 0.554 | 0.297 | 0.336155897331 | gnomAD-4.0.0 | 9.29568E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27143E-05 | 0 | 0 |
| A/T | rs199647622 |
-0.388 | 1.0 | N | 0.587 | 0.314 | 0.386721274199 | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | I | None | 4.13E-05 | 2.54439E-04 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 2.34E-05 | 1.40331E-04 |
| A/T | rs199647622 |
-0.388 | 1.0 | N | 0.587 | 0.314 | 0.386721274199 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.42E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs199647622 |
-0.388 | 1.0 | N | 0.587 | 0.314 | 0.386721274199 | gnomAD-4.0.0 | 2.54082E-05 | None | None | None | None | I | None | 2.67115E-05 | 1.66711E-04 | None | 0 | 0 | None | 0 | 0 | 1.61047E-05 | 9.88077E-05 | 1.60102E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7348 | likely_pathogenic | 0.6288 | pathogenic | -0.51 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/D | 0.8405 | likely_pathogenic | 0.676 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.448098784 | None | None | I |
| A/E | 0.7703 | likely_pathogenic | 0.5843 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| A/F | 0.6946 | likely_pathogenic | 0.548 | ambiguous | -0.781 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| A/G | 0.2938 | likely_benign | 0.2151 | benign | -0.781 | Destabilizing | 1.0 | D | 0.535 | neutral | N | 0.448984218 | None | None | I |
| A/H | 0.829 | likely_pathogenic | 0.7226 | pathogenic | -0.724 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| A/I | 0.5506 | ambiguous | 0.3972 | ambiguous | -0.221 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| A/K | 0.8747 | likely_pathogenic | 0.7523 | pathogenic | -0.78 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| A/L | 0.3896 | ambiguous | 0.2801 | benign | -0.221 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | I |
| A/M | 0.5295 | ambiguous | 0.4033 | ambiguous | -0.332 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| A/N | 0.571 | likely_pathogenic | 0.4498 | ambiguous | -0.484 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| A/P | 0.5289 | ambiguous | 0.4026 | ambiguous | -0.305 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.470476998 | None | None | I |
| A/Q | 0.6533 | likely_pathogenic | 0.5276 | ambiguous | -0.646 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| A/R | 0.753 | likely_pathogenic | 0.6101 | pathogenic | -0.409 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| A/S | 0.138 | likely_benign | 0.1131 | benign | -0.775 | Destabilizing | 1.0 | D | 0.554 | neutral | N | 0.411753981 | None | None | I |
| A/T | 0.2063 | likely_benign | 0.1415 | benign | -0.728 | Destabilizing | 1.0 | D | 0.587 | neutral | N | 0.440866167 | None | None | I |
| A/V | 0.2966 | likely_benign | 0.1948 | benign | -0.305 | Destabilizing | 1.0 | D | 0.554 | neutral | N | 0.421088328 | None | None | I |
| A/W | 0.9435 | likely_pathogenic | 0.8921 | pathogenic | -1.066 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | I |
| A/Y | 0.8206 | likely_pathogenic | 0.7093 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
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.