Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24601 | 74026;74027;74028 | chr2:178572331;178572330;178572329 | chr2:179437058;179437057;179437056 |
| N2AB | 22960 | 69103;69104;69105 | chr2:178572331;178572330;178572329 | chr2:179437058;179437057;179437056 |
| N2A | 22033 | 66322;66323;66324 | chr2:178572331;178572330;178572329 | chr2:179437058;179437057;179437056 |
| N2B | 15536 | 46831;46832;46833 | chr2:178572331;178572330;178572329 | chr2:179437058;179437057;179437056 |
| Novex-1 | 15661 | 47206;47207;47208 | chr2:178572331;178572330;178572329 | chr2:179437058;179437057;179437056 |
| Novex-2 | 15728 | 47407;47408;47409 | chr2:178572331;178572330;178572329 | chr2:179437058;179437057;179437056 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1021628897  |
-0.826 | 0.06 | N | 0.692 | 0.282 | 0.576839456108 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87853E-04 | 0 | 0 |
| I/T | rs1021628897 |
-0.826 | 0.06 | N | 0.692 | 0.282 | 0.576839456108 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| I/T | rs1021628897 |
-0.826 | 0.06 | N | 0.692 | 0.282 | 0.576839456108 | gnomAD-4.0.0 | 1.86137E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.23744E-05 | None | 1.56274E-05 | 0 | 0 | 1.09835E-05 | 0 |
| I/V | None | None | None | N | 0.279 | 0.063 | 0.283761946502 | gnomAD-4.0.0 | 6.85229E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00891E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4329 | ambiguous | 0.2642 | benign | -1.187 | Destabilizing | 0.221 | N | 0.653 | neutral | None | None | None | None | I |
| I/C | 0.7571 | likely_pathogenic | 0.6609 | pathogenic | -1.013 | Destabilizing | 0.938 | D | 0.751 | deleterious | None | None | None | None | I |
| I/D | 0.947 | likely_pathogenic | 0.8852 | pathogenic | -0.183 | Destabilizing | 0.801 | D | 0.817 | deleterious | None | None | None | None | I |
| I/E | 0.8805 | likely_pathogenic | 0.7753 | pathogenic | -0.22 | Destabilizing | 0.748 | D | 0.811 | deleterious | None | None | None | None | I |
| I/F | 0.3821 | ambiguous | 0.269 | benign | -0.89 | Destabilizing | 0.373 | N | 0.753 | deleterious | N | 0.479420181 | None | None | I |
| I/G | 0.8676 | likely_pathogenic | 0.7172 | pathogenic | -1.434 | Destabilizing | 0.801 | D | 0.8 | deleterious | None | None | None | None | I |
| I/H | 0.8725 | likely_pathogenic | 0.7597 | pathogenic | -0.505 | Destabilizing | 0.95 | D | 0.812 | deleterious | None | None | None | None | I |
| I/K | 0.7635 | likely_pathogenic | 0.6494 | pathogenic | -0.605 | Destabilizing | 0.106 | N | 0.81 | deleterious | None | None | None | None | I |
| I/L | 0.2024 | likely_benign | 0.1365 | benign | -0.622 | Destabilizing | 0.001 | N | 0.39 | neutral | N | 0.498892963 | None | None | I |
| I/M | 0.1844 | likely_benign | 0.1357 | benign | -0.619 | Destabilizing | 0.152 | N | 0.748 | deleterious | N | 0.499375753 | None | None | I |
| I/N | 0.7199 | likely_pathogenic | 0.5259 | ambiguous | -0.459 | Destabilizing | 0.902 | D | 0.815 | deleterious | N | 0.481520094 | None | None | I |
| I/P | 0.7092 | likely_pathogenic | 0.5668 | pathogenic | -0.777 | Destabilizing | 0.925 | D | 0.818 | deleterious | None | None | None | None | I |
| I/Q | 0.8035 | likely_pathogenic | 0.664 | pathogenic | -0.655 | Destabilizing | 0.836 | D | 0.809 | deleterious | None | None | None | None | I |
| I/R | 0.6415 | likely_pathogenic | 0.509 | ambiguous | -0.027 | Destabilizing | 0.616 | D | 0.812 | deleterious | None | None | None | None | I |
| I/S | 0.5787 | likely_pathogenic | 0.3733 | ambiguous | -1.113 | Destabilizing | 0.6 | D | 0.776 | deleterious | N | 0.511899546 | None | None | I |
| I/T | 0.2299 | likely_benign | 0.1484 | benign | -1.028 | Destabilizing | 0.06 | N | 0.692 | prob.neutral | N | 0.49923968 | None | None | I |
| I/V | 0.0711 | likely_benign | 0.064 | benign | -0.777 | Destabilizing | None | N | 0.279 | neutral | N | 0.429206379 | None | None | I |
| I/W | 0.9136 | likely_pathogenic | 0.8578 | pathogenic | -0.84 | Destabilizing | 0.986 | D | 0.775 | deleterious | None | None | None | None | I |
| I/Y | 0.8143 | likely_pathogenic | 0.699 | pathogenic | -0.618 | Destabilizing | 0.158 | N | 0.758 | deleterious | 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.