Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26517 | 79774;79775;79776 | chr2:178566583;178566582;178566581 | chr2:179431310;179431309;179431308 |
| N2AB | 24876 | 74851;74852;74853 | chr2:178566583;178566582;178566581 | chr2:179431310;179431309;179431308 |
| N2A | 23949 | 72070;72071;72072 | chr2:178566583;178566582;178566581 | chr2:179431310;179431309;179431308 |
| N2B | 17452 | 52579;52580;52581 | chr2:178566583;178566582;178566581 | chr2:179431310;179431309;179431308 |
| Novex-1 | 17577 | 52954;52955;52956 | chr2:178566583;178566582;178566581 | chr2:179431310;179431309;179431308 |
| Novex-2 | 17644 | 53155;53156;53157 | chr2:178566583;178566582;178566581 | chr2:179431310;179431309;179431308 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.309 | N | 0.53 | 0.13 | 0.16115917748 | gnomAD-4.0.0 | 6.84635E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99525E-07 | 0 | 0 |
| S/R | rs1559352866  |
None | 0.939 | N | 0.639 | 0.311 | 0.270447802918 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| S/R | rs1559352866 |
None | 0.939 | N | 0.639 | 0.311 | 0.270447802918 | gnomAD-4.0.0 | 1.36927E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79905E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0895 | likely_benign | 0.0883 | benign | -0.628 | Destabilizing | 0.004 | N | 0.32 | neutral | None | None | None | None | I |
| S/C | 0.0601 | likely_benign | 0.0627 | benign | -0.454 | Destabilizing | 0.007 | N | 0.405 | neutral | N | 0.500551976 | None | None | I |
| S/D | 0.6626 | likely_pathogenic | 0.6986 | pathogenic | -0.498 | Destabilizing | 0.854 | D | 0.614 | neutral | None | None | None | None | I |
| S/E | 0.7666 | likely_pathogenic | 0.7822 | pathogenic | -0.542 | Destabilizing | 0.742 | D | 0.611 | neutral | None | None | None | None | I |
| S/F | 0.3457 | ambiguous | 0.3375 | benign | -0.991 | Destabilizing | 0.91 | D | 0.664 | neutral | None | None | None | None | I |
| S/G | 0.0996 | likely_benign | 0.1013 | benign | -0.823 | Destabilizing | 0.309 | N | 0.53 | neutral | N | 0.470489276 | None | None | I |
| S/H | 0.5783 | likely_pathogenic | 0.6168 | pathogenic | -1.361 | Destabilizing | 0.996 | D | 0.623 | neutral | None | None | None | None | I |
| S/I | 0.3718 | ambiguous | 0.3434 | ambiguous | -0.227 | Destabilizing | 0.521 | D | 0.638 | neutral | N | 0.503035072 | None | None | I |
| S/K | 0.8966 | likely_pathogenic | 0.9105 | pathogenic | -0.738 | Destabilizing | 0.742 | D | 0.588 | neutral | None | None | None | None | I |
| S/L | 0.1356 | likely_benign | 0.1225 | benign | -0.227 | Destabilizing | 0.009 | N | 0.445 | neutral | None | None | None | None | I |
| S/M | 0.2182 | likely_benign | 0.2094 | benign | 0.207 | Stabilizing | 0.91 | D | 0.641 | neutral | None | None | None | None | I |
| S/N | 0.2538 | likely_benign | 0.2706 | benign | -0.624 | Destabilizing | 0.815 | D | 0.634 | neutral | N | 0.496451706 | None | None | I |
| S/P | 0.9552 | likely_pathogenic | 0.9643 | pathogenic | -0.329 | Destabilizing | 0.953 | D | 0.64 | neutral | None | None | None | None | I |
| S/Q | 0.6816 | likely_pathogenic | 0.7141 | pathogenic | -0.905 | Destabilizing | 0.953 | D | 0.625 | neutral | None | None | None | None | I |
| S/R | 0.8303 | likely_pathogenic | 0.8528 | pathogenic | -0.506 | Destabilizing | 0.939 | D | 0.639 | neutral | N | 0.48207998 | None | None | I |
| S/T | 0.137 | likely_benign | 0.1266 | benign | -0.655 | Destabilizing | 0.472 | N | 0.546 | neutral | N | 0.488956515 | None | None | I |
| S/V | 0.2961 | likely_benign | 0.2782 | benign | -0.329 | Destabilizing | 0.373 | N | 0.613 | neutral | None | None | None | None | I |
| S/W | 0.5233 | ambiguous | 0.5417 | ambiguous | -0.95 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | I |
| S/Y | 0.3237 | likely_benign | 0.336 | benign | -0.69 | Destabilizing | 0.984 | D | 0.677 | prob.neutral | None | None | 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.