Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22318 | 67177;67178;67179 | chr2:178580427;178580426;178580425 | chr2:179445154;179445153;179445152 |
| N2AB | 20677 | 62254;62255;62256 | chr2:178580427;178580426;178580425 | chr2:179445154;179445153;179445152 |
| N2A | 19750 | 59473;59474;59475 | chr2:178580427;178580426;178580425 | chr2:179445154;179445153;179445152 |
| N2B | 13253 | 39982;39983;39984 | chr2:178580427;178580426;178580425 | chr2:179445154;179445153;179445152 |
| Novex-1 | 13378 | 40357;40358;40359 | chr2:178580427;178580426;178580425 | chr2:179445154;179445153;179445152 |
| Novex-2 | 13445 | 40558;40559;40560 | chr2:178580427;178580426;178580425 | chr2:179445154;179445153;179445152 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1282369228  |
-1.529 | 0.003 | N | 0.133 | 0.239 | 0.450441870249 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1282369228 |
-1.529 | 0.003 | N | 0.133 | 0.239 | 0.450441870249 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs1282369228 |
-1.529 | 0.003 | N | 0.133 | 0.239 | 0.450441870249 | gnomAD-4.0.0 | 3.09963E-06 | None | None | None | None | N | None | 1.33572E-05 | 3.33556E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20369E-05 |
| F/S | None | None | 0.028 | N | 0.361 | 0.356 | 0.534907319155 | gnomAD-4.0.0 | 4.77734E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58109E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6188 | likely_pathogenic | 0.6859 | pathogenic | -2.819 | Highly Destabilizing | 0.373 | N | 0.467 | neutral | None | None | None | None | N |
| F/C | 0.4208 | ambiguous | 0.4871 | ambiguous | -1.556 | Destabilizing | 0.994 | D | 0.596 | neutral | N | 0.452289174 | None | None | N |
| F/D | 0.9139 | likely_pathogenic | 0.9355 | pathogenic | -2.689 | Highly Destabilizing | 0.91 | D | 0.621 | neutral | None | None | None | None | N |
| F/E | 0.8569 | likely_pathogenic | 0.8826 | pathogenic | -2.523 | Highly Destabilizing | 0.742 | D | 0.612 | neutral | None | None | None | None | N |
| F/G | 0.8975 | likely_pathogenic | 0.9264 | pathogenic | -3.225 | Highly Destabilizing | 0.59 | D | 0.554 | neutral | None | None | None | None | N |
| F/H | 0.6095 | likely_pathogenic | 0.6604 | pathogenic | -1.595 | Destabilizing | 0.953 | D | 0.566 | neutral | None | None | None | None | N |
| F/I | 0.3036 | likely_benign | 0.3446 | ambiguous | -1.518 | Destabilizing | 0.521 | D | 0.433 | neutral | N | 0.403284506 | None | None | N |
| F/K | 0.9277 | likely_pathogenic | 0.9422 | pathogenic | -1.901 | Destabilizing | 0.742 | D | 0.589 | neutral | None | None | None | None | N |
| F/L | 0.827 | likely_pathogenic | 0.8472 | pathogenic | -1.518 | Destabilizing | 0.003 | N | 0.133 | neutral | N | 0.395395741 | None | None | N |
| F/M | 0.4655 | ambiguous | 0.4951 | ambiguous | -1.095 | Destabilizing | 0.91 | D | 0.553 | neutral | None | None | None | None | N |
| F/N | 0.7281 | likely_pathogenic | 0.7727 | pathogenic | -2.201 | Highly Destabilizing | 0.91 | D | 0.621 | neutral | None | None | None | None | N |
| F/P | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -1.958 | Destabilizing | 0.953 | D | 0.627 | neutral | None | None | None | None | N |
| F/Q | 0.7738 | likely_pathogenic | 0.8073 | pathogenic | -2.232 | Highly Destabilizing | 0.91 | D | 0.631 | neutral | None | None | None | None | N |
| F/R | 0.8692 | likely_pathogenic | 0.8936 | pathogenic | -1.27 | Destabilizing | 0.91 | D | 0.62 | neutral | None | None | None | None | N |
| F/S | 0.4463 | ambiguous | 0.525 | ambiguous | -2.89 | Highly Destabilizing | 0.028 | N | 0.361 | neutral | N | 0.371958734 | None | None | N |
| F/T | 0.5057 | ambiguous | 0.5791 | pathogenic | -2.626 | Highly Destabilizing | 0.59 | D | 0.545 | neutral | None | None | None | None | N |
| F/V | 0.28 | likely_benign | 0.3196 | benign | -1.958 | Destabilizing | 0.309 | N | 0.457 | neutral | N | 0.433914057 | None | None | N |
| F/W | 0.5841 | likely_pathogenic | 0.6255 | pathogenic | -0.531 | Destabilizing | 0.996 | D | 0.547 | neutral | None | None | None | None | N |
| F/Y | 0.168 | likely_benign | 0.1774 | benign | -0.872 | Destabilizing | 0.028 | N | 0.211 | neutral | N | 0.48426552 | 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.