Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7526 | 22801;22802;22803 | chr2:178722087;178722086;178722085 | chr2:179586814;179586813;179586812 |
| N2AB | 7209 | 21850;21851;21852 | chr2:178722087;178722086;178722085 | chr2:179586814;179586813;179586812 |
| N2A | 6282 | 19069;19070;19071 | chr2:178722087;178722086;178722085 | chr2:179586814;179586813;179586812 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/D | None | None | 0.667 | D | 0.688 | 0.62 | 0.885774903276 | gnomAD-4.0.0 | 1.60858E-06 | None | None | None | None | N | None | 0 | 2.30574E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | rs754972548  |
-1.521 | 0.497 | D | 0.664 | 0.571 | 0.779041191306 | gnomAD-2.1.1 | 4.1E-05 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.13E-05 | 0 |
| V/F | rs754972548 |
-1.521 | 0.497 | D | 0.664 | 0.571 | 0.779041191306 | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| V/F | rs754972548 |
-1.521 | 0.497 | D | 0.664 | 0.571 | 0.779041191306 | gnomAD-4.0.0 | 7.90152E-05 | None | None | None | None | N | None | 4.01273E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.05416E-04 | 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 | 0.1827 | likely_benign | 0.1801 | benign | -1.806 | Destabilizing | 0.001 | N | 0.307 | neutral | N | 0.502278064 | None | None | N |
| V/C | 0.7352 | likely_pathogenic | 0.7749 | pathogenic | -1.416 | Destabilizing | 0.968 | D | 0.613 | neutral | None | None | None | None | N |
| V/D | 0.5967 | likely_pathogenic | 0.6237 | pathogenic | -1.763 | Destabilizing | 0.667 | D | 0.688 | prob.neutral | D | 0.545474321 | None | None | N |
| V/E | 0.5325 | ambiguous | 0.5856 | pathogenic | -1.68 | Destabilizing | 0.567 | D | 0.646 | neutral | None | None | None | None | N |
| V/F | 0.2438 | likely_benign | 0.3362 | benign | -1.21 | Destabilizing | 0.497 | N | 0.664 | neutral | D | 0.526609598 | None | None | N |
| V/G | 0.2605 | likely_benign | 0.245 | benign | -2.217 | Highly Destabilizing | 0.124 | N | 0.659 | neutral | N | 0.510733842 | None | None | N |
| V/H | 0.7369 | likely_pathogenic | 0.8189 | pathogenic | -1.762 | Destabilizing | 0.968 | D | 0.663 | neutral | None | None | None | None | N |
| V/I | 0.0743 | likely_benign | 0.0872 | benign | -0.734 | Destabilizing | 0.001 | N | 0.207 | neutral | N | 0.503067498 | None | None | N |
| V/K | 0.5584 | ambiguous | 0.6157 | pathogenic | -1.429 | Destabilizing | 0.567 | D | 0.648 | neutral | None | None | None | None | N |
| V/L | 0.2058 | likely_benign | 0.3121 | benign | -0.734 | Destabilizing | 0.02 | N | 0.487 | neutral | D | 0.532390327 | None | None | N |
| V/M | 0.1449 | likely_benign | 0.183 | benign | -0.731 | Destabilizing | 0.567 | D | 0.572 | neutral | None | None | None | None | N |
| V/N | 0.4277 | ambiguous | 0.4826 | ambiguous | -1.379 | Destabilizing | 0.726 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/P | 0.9215 | likely_pathogenic | 0.9353 | pathogenic | -1.059 | Destabilizing | 0.726 | D | 0.66 | neutral | None | None | None | None | N |
| V/Q | 0.5069 | ambiguous | 0.5862 | pathogenic | -1.446 | Destabilizing | 0.726 | D | 0.647 | neutral | None | None | None | None | N |
| V/R | 0.4947 | ambiguous | 0.5685 | pathogenic | -1.048 | Destabilizing | 0.726 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/S | 0.278 | likely_benign | 0.2935 | benign | -2.01 | Highly Destabilizing | 0.157 | N | 0.621 | neutral | None | None | None | None | N |
| V/T | 0.1938 | likely_benign | 0.1947 | benign | -1.804 | Destabilizing | 0.005 | N | 0.367 | neutral | None | None | None | None | N |
| V/W | 0.899 | likely_pathogenic | 0.9461 | pathogenic | -1.485 | Destabilizing | 0.968 | D | 0.649 | neutral | None | None | None | None | N |
| V/Y | 0.6957 | likely_pathogenic | 0.7865 | pathogenic | -1.168 | Destabilizing | 0.726 | D | 0.633 | 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.