Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14057 | 42394;42395;42396 | chr2:178634612;178634611;178634610 | chr2:179499339;179499338;179499337 |
| N2AB | 12416 | 37471;37472;37473 | chr2:178634612;178634611;178634610 | chr2:179499339;179499338;179499337 |
| N2A | 11489 | 34690;34691;34692 | chr2:178634612;178634611;178634610 | chr2:179499339;179499338;179499337 |
| N2B | 4992 | 15199;15200;15201 | chr2:178634612;178634611;178634610 | chr2:179499339;179499338;179499337 |
| Novex-1 | 5117 | 15574;15575;15576 | chr2:178634612;178634611;178634610 | chr2:179499339;179499338;179499337 |
| Novex-2 | 5184 | 15775;15776;15777 | chr2:178634612;178634611;178634610 | chr2:179499339;179499338;179499337 |
| 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/T | rs376192503  |
-0.548 | 0.248 | N | 0.243 | 0.21 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/T | rs376192503 |
-0.548 | 0.248 | N | 0.243 | 0.21 | None | gnomAD-4.0.0 | 8.21326E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89646E-06 | 0 | 1.65761E-05 |
| A/V | rs900184988 |
None | 0.122 | N | 0.142 | 0.153 | 0.213573922156 | 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 |
| A/V | rs900184988 |
None | 0.122 | N | 0.142 | 0.153 | 0.213573922156 | gnomAD-4.0.0 | 5.07522E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.02489E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7686 | likely_pathogenic | 0.7494 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.491 | neutral | None | None | None | None | N |
| A/D | 0.7789 | likely_pathogenic | 0.7484 | pathogenic | -0.844 | Destabilizing | 0.994 | D | 0.597 | neutral | N | 0.448925829 | None | None | N |
| A/E | 0.6721 | likely_pathogenic | 0.6472 | pathogenic | -0.957 | Destabilizing | 0.996 | D | 0.489 | neutral | None | None | None | None | N |
| A/F | 0.7138 | likely_pathogenic | 0.7072 | pathogenic | -0.965 | Destabilizing | 0.996 | D | 0.601 | neutral | None | None | None | None | N |
| A/G | 0.4547 | ambiguous | 0.4211 | ambiguous | -0.752 | Destabilizing | 0.98 | D | 0.451 | neutral | N | 0.438898942 | None | None | N |
| A/H | 0.8239 | likely_pathogenic | 0.8146 | pathogenic | -0.812 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| A/I | 0.4583 | ambiguous | 0.448 | ambiguous | -0.418 | Destabilizing | 0.942 | D | 0.483 | neutral | None | None | None | None | N |
| A/K | 0.8671 | likely_pathogenic | 0.8461 | pathogenic | -1.083 | Destabilizing | 0.991 | D | 0.486 | neutral | None | None | None | None | N |
| A/L | 0.389 | ambiguous | 0.3463 | ambiguous | -0.418 | Destabilizing | 0.871 | D | 0.508 | neutral | None | None | None | None | N |
| A/M | 0.4785 | ambiguous | 0.4611 | ambiguous | -0.374 | Destabilizing | 0.996 | D | 0.554 | neutral | None | None | None | None | N |
| A/N | 0.6678 | likely_pathogenic | 0.6328 | pathogenic | -0.726 | Destabilizing | 0.996 | D | 0.617 | neutral | None | None | None | None | N |
| A/P | 0.8465 | likely_pathogenic | 0.8186 | pathogenic | -0.445 | Destabilizing | 0.998 | D | 0.534 | neutral | N | 0.451396511 | None | None | N |
| A/Q | 0.6809 | likely_pathogenic | 0.6611 | pathogenic | -0.978 | Destabilizing | 0.999 | D | 0.543 | neutral | None | None | None | None | N |
| A/R | 0.7822 | likely_pathogenic | 0.7781 | pathogenic | -0.581 | Destabilizing | 0.996 | D | 0.545 | neutral | None | None | None | None | N |
| A/S | 0.1649 | likely_benign | 0.1644 | benign | -0.964 | Destabilizing | 0.925 | D | 0.483 | neutral | N | 0.439647235 | None | None | N |
| A/T | 0.1729 | likely_benign | 0.1742 | benign | -0.996 | Destabilizing | 0.248 | N | 0.243 | neutral | N | 0.350423939 | None | None | N |
| A/V | 0.231 | likely_benign | 0.2379 | benign | -0.445 | Destabilizing | 0.122 | N | 0.142 | neutral | N | 0.367808782 | None | None | N |
| A/W | 0.9535 | likely_pathogenic | 0.9487 | pathogenic | -1.179 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| A/Y | 0.8425 | likely_pathogenic | 0.8237 | pathogenic | -0.834 | Destabilizing | 0.999 | D | 0.611 | 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.