Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27720 | 83383;83384;83385 | chr2:178562974;178562973;178562972 | chr2:179427701;179427700;179427699 |
| N2AB | 26079 | 78460;78461;78462 | chr2:178562974;178562973;178562972 | chr2:179427701;179427700;179427699 |
| N2A | 25152 | 75679;75680;75681 | chr2:178562974;178562973;178562972 | chr2:179427701;179427700;179427699 |
| N2B | 18655 | 56188;56189;56190 | chr2:178562974;178562973;178562972 | chr2:179427701;179427700;179427699 |
| Novex-1 | 18780 | 56563;56564;56565 | chr2:178562974;178562973;178562972 | chr2:179427701;179427700;179427699 |
| Novex-2 | 18847 | 56764;56765;56766 | chr2:178562974;178562973;178562972 | chr2:179427701;179427700;179427699 |
| 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/D | rs753972441  |
-0.802 | 0.999 | N | 0.722 | 0.539 | 0.631088956699 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/D | rs753972441 |
-0.802 | 0.999 | N | 0.722 | 0.539 | 0.631088956699 | gnomAD-4.0.0 | 6.84259E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99494E-07 | 0 | 0 |
| A/S | None | None | 0.992 | N | 0.485 | 0.328 | 0.410204130746 | gnomAD-4.0.0 | 1.59151E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85851E-06 | 0 | 0 |
| A/V | rs753972441 |
None | 0.996 | N | 0.547 | 0.302 | None | gnomAD-4.0.0 | 2.05278E-06 | None | None | None | None | N | None | 0 | 2.23644E-05 | None | 0 | 0 | None | 0 | 0 | 8.99494E-07 | 0 | 1.65684E-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 | 0.5268 | ambiguous | 0.5053 | ambiguous | -0.882 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/D | 0.9305 | likely_pathogenic | 0.9159 | pathogenic | -1.122 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | N | 0.503013797 | None | None | N |
| A/E | 0.8715 | likely_pathogenic | 0.8442 | pathogenic | -1.15 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| A/F | 0.7781 | likely_pathogenic | 0.7577 | pathogenic | -0.924 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| A/G | 0.2267 | likely_benign | 0.2327 | benign | -1.086 | Destabilizing | 0.998 | D | 0.534 | neutral | N | 0.518647452 | None | None | N |
| A/H | 0.8914 | likely_pathogenic | 0.8757 | pathogenic | -1.32 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/I | 0.6154 | likely_pathogenic | 0.5711 | pathogenic | -0.279 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/K | 0.9387 | likely_pathogenic | 0.9292 | pathogenic | -1.304 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| A/L | 0.5549 | ambiguous | 0.507 | ambiguous | -0.279 | Destabilizing | 0.997 | D | 0.619 | neutral | None | None | None | None | N |
| A/M | 0.5866 | likely_pathogenic | 0.5468 | ambiguous | -0.275 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/N | 0.803 | likely_pathogenic | 0.782 | pathogenic | -1.006 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| A/P | 0.8453 | likely_pathogenic | 0.811 | pathogenic | -0.42 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.503013797 | None | None | N |
| A/Q | 0.8162 | likely_pathogenic | 0.7972 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| A/R | 0.908 | likely_pathogenic | 0.8991 | pathogenic | -0.966 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/S | 0.1561 | likely_benign | 0.1526 | benign | -1.327 | Destabilizing | 0.992 | D | 0.485 | neutral | N | 0.494264385 | None | None | N |
| A/T | 0.2393 | likely_benign | 0.2056 | benign | -1.257 | Destabilizing | 0.884 | D | 0.346 | neutral | N | 0.513894993 | None | None | N |
| A/V | 0.3054 | likely_benign | 0.2756 | benign | -0.42 | Destabilizing | 0.996 | D | 0.547 | neutral | N | 0.480491709 | None | None | N |
| A/W | 0.9573 | likely_pathogenic | 0.9497 | pathogenic | -1.295 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| A/Y | 0.844 | likely_pathogenic | 0.8182 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.749 | deleterious | 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.