Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31269 | 94030;94031;94032 | chr2:178547821;178547820;178547819 | chr2:179412548;179412547;179412546 |
| N2AB | 29628 | 89107;89108;89109 | chr2:178547821;178547820;178547819 | chr2:179412548;179412547;179412546 |
| N2A | 28701 | 86326;86327;86328 | chr2:178547821;178547820;178547819 | chr2:179412548;179412547;179412546 |
| N2B | 22204 | 66835;66836;66837 | chr2:178547821;178547820;178547819 | chr2:179412548;179412547;179412546 |
| Novex-1 | 22329 | 67210;67211;67212 | chr2:178547821;178547820;178547819 | chr2:179412548;179412547;179412546 |
| Novex-2 | 22396 | 67411;67412;67413 | chr2:178547821;178547820;178547819 | chr2:179412548;179412547;179412546 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 0.822 | N | 0.579 | 0.38 | 0.277730125212 | gnomAD-4.0.0 | 1.59112E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77423E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs368404585  |
0.231 | 0.942 | N | 0.737 | 0.503 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/V | rs368404585 |
0.231 | 0.942 | N | 0.737 | 0.503 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/V | rs368404585 |
0.231 | 0.942 | N | 0.737 | 0.503 | None | gnomAD-4.0.0 | 1.31416E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.93997E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1896 | likely_benign | 0.1854 | benign | -0.453 | Destabilizing | 0.698 | D | 0.643 | neutral | N | 0.483841445 | None | None | N |
| D/C | 0.5898 | likely_pathogenic | 0.5921 | pathogenic | -0.081 | Destabilizing | 0.998 | D | 0.75 | deleterious | None | None | None | None | N |
| D/E | 0.1236 | likely_benign | 0.1156 | benign | -0.412 | Destabilizing | 0.006 | N | 0.273 | neutral | N | 0.432740621 | None | None | N |
| D/F | 0.5421 | ambiguous | 0.5361 | ambiguous | -0.332 | Destabilizing | 0.993 | D | 0.751 | deleterious | None | None | None | None | N |
| D/G | 0.1457 | likely_benign | 0.1472 | benign | -0.679 | Destabilizing | 0.822 | D | 0.579 | neutral | N | 0.422427627 | None | None | N |
| D/H | 0.279 | likely_benign | 0.2786 | benign | -0.307 | Destabilizing | 0.992 | D | 0.647 | neutral | N | 0.512492271 | None | None | N |
| D/I | 0.3406 | ambiguous | 0.3272 | benign | 0.103 | Stabilizing | 0.978 | D | 0.76 | deleterious | None | None | None | None | N |
| D/K | 0.3722 | ambiguous | 0.3714 | ambiguous | 0.07 | Stabilizing | 0.754 | D | 0.559 | neutral | None | None | None | None | N |
| D/L | 0.339 | likely_benign | 0.3362 | benign | 0.103 | Stabilizing | 0.956 | D | 0.741 | deleterious | None | None | None | None | N |
| D/M | 0.5088 | ambiguous | 0.497 | ambiguous | 0.314 | Stabilizing | 0.998 | D | 0.748 | deleterious | None | None | None | None | N |
| D/N | 0.1068 | likely_benign | 0.101 | benign | -0.253 | Destabilizing | 0.822 | D | 0.585 | neutral | N | 0.437762439 | None | None | N |
| D/P | 0.772 | likely_pathogenic | 0.803 | pathogenic | -0.06 | Destabilizing | 0.978 | D | 0.644 | neutral | None | None | None | None | N |
| D/Q | 0.2809 | likely_benign | 0.2712 | benign | -0.206 | Destabilizing | 0.915 | D | 0.595 | neutral | None | None | None | None | N |
| D/R | 0.4138 | ambiguous | 0.427 | ambiguous | 0.238 | Stabilizing | 0.956 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/S | 0.1412 | likely_benign | 0.1364 | benign | -0.373 | Destabilizing | 0.754 | D | 0.549 | neutral | None | None | None | None | N |
| D/T | 0.1857 | likely_benign | 0.1794 | benign | -0.199 | Destabilizing | 0.956 | D | 0.597 | neutral | None | None | None | None | N |
| D/V | 0.2037 | likely_benign | 0.1944 | benign | -0.06 | Destabilizing | 0.942 | D | 0.737 | prob.delet. | N | 0.493559794 | None | None | N |
| D/W | 0.7924 | likely_pathogenic | 0.805 | pathogenic | -0.175 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2017 | likely_benign | 0.2048 | benign | -0.103 | Destabilizing | 0.99 | D | 0.752 | deleterious | N | 0.462487525 | 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.