Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27772 | 83539;83540;83541 | chr2:178562818;178562817;178562816 | chr2:179427545;179427544;179427543 |
| N2AB | 26131 | 78616;78617;78618 | chr2:178562818;178562817;178562816 | chr2:179427545;179427544;179427543 |
| N2A | 25204 | 75835;75836;75837 | chr2:178562818;178562817;178562816 | chr2:179427545;179427544;179427543 |
| N2B | 18707 | 56344;56345;56346 | chr2:178562818;178562817;178562816 | chr2:179427545;179427544;179427543 |
| Novex-1 | 18832 | 56719;56720;56721 | chr2:178562818;178562817;178562816 | chr2:179427545;179427544;179427543 |
| Novex-2 | 18899 | 56920;56921;56922 | chr2:178562818;178562817;178562816 | chr2:179427545;179427544;179427543 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs578191491  |
0.363 | 1.0 | D | 0.767 | 0.546 | 0.766716802719 | gnomAD-2.1.1 | 5.24538E-04 | None | None | None | None | I | None | 8.33E-05 | 2.92813E-03 | None | 0 | 0 | None | 0 | None | 0 | 2.59695E-04 | 1.13122E-03 |
| N/I | rs578191491 |
0.363 | 1.0 | D | 0.767 | 0.546 | 0.766716802719 | gnomAD-3.1.2 | 1.27529E-03 | None | None | None | None | I | None | 9.65E-05 | 1.08183E-02 | 0 | 0 | 0 | None | 0 | 0 | 3.23406E-04 | 2.07125E-04 | 9.5511E-04 |
| N/I | rs578191491 |
0.363 | 1.0 | D | 0.767 | 0.546 | 0.766716802719 | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 0 | None |
| N/I | rs578191491 |
0.363 | 1.0 | D | 0.767 | 0.546 | 0.766716802719 | gnomAD-4.0.0 | 3.48394E-04 | None | None | None | None | I | None | 7.99851E-05 | 4.89067E-03 | None | 0 | 0 | None | 0 | 1.65017E-04 | 2.00076E-04 | 1.0983E-05 | 4.00551E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2391 | likely_benign | 0.2424 | benign | -0.345 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| N/C | 0.307 | likely_benign | 0.3123 | benign | 0.278 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/D | 0.1608 | likely_benign | 0.1663 | benign | 0.102 | Stabilizing | 0.999 | D | 0.591 | neutral | N | 0.491991208 | None | None | I |
| N/E | 0.4547 | ambiguous | 0.4629 | ambiguous | 0.073 | Stabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | I |
| N/F | 0.556 | ambiguous | 0.5575 | ambiguous | -0.662 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| N/G | 0.2508 | likely_benign | 0.2528 | benign | -0.529 | Destabilizing | 0.999 | D | 0.542 | neutral | None | None | None | None | I |
| N/H | 0.1157 | likely_benign | 0.1187 | benign | -0.522 | Destabilizing | 1.0 | D | 0.63 | neutral | N | 0.490343002 | None | None | I |
| N/I | 0.4203 | ambiguous | 0.4189 | ambiguous | 0.053 | Stabilizing | 1.0 | D | 0.767 | deleterious | D | 0.525879949 | None | None | I |
| N/K | 0.3348 | likely_benign | 0.3317 | benign | 0.061 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.518697806 | None | None | I |
| N/L | 0.3141 | likely_benign | 0.322 | benign | 0.053 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| N/M | 0.4037 | ambiguous | 0.4142 | ambiguous | 0.36 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| N/P | 0.7929 | likely_pathogenic | 0.8025 | pathogenic | -0.053 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| N/Q | 0.3224 | likely_benign | 0.3234 | benign | -0.44 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| N/R | 0.3872 | ambiguous | 0.3964 | ambiguous | 0.116 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| N/S | 0.1013 | likely_benign | 0.1044 | benign | -0.217 | Destabilizing | 0.999 | D | 0.541 | neutral | N | 0.516716294 | None | None | I |
| N/T | 0.2074 | likely_benign | 0.2117 | benign | -0.1 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.493950627 | None | None | I |
| N/V | 0.3987 | ambiguous | 0.4 | ambiguous | -0.053 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| N/W | 0.8391 | likely_pathogenic | 0.8504 | pathogenic | -0.625 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/Y | 0.229 | likely_benign | 0.2378 | benign | -0.368 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.526640418 | None | None | I |
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.