Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3016 | 9271;9272;9273 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
| N2AB | 3016 | 9271;9272;9273 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
| N2A | 3016 | 9271;9272;9273 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
| N2B | 2970 | 9133;9134;9135 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
| Novex-1 | 2970 | 9133;9134;9135 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
| Novex-2 | 2970 | 9133;9134;9135 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
| Novex-3 | 3016 | 9271;9272;9273 | chr2:178768790;178768789;178768788 | chr2:179633517;179633516;179633515 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | rs1223583950  |
None | 0.049 | D | 0.547 | 0.339 | 0.449572021084 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/K | rs1223583950 |
None | 0.049 | D | 0.547 | 0.339 | 0.449572021084 | gnomAD-4.0.0 | 6.57237E-06 | None | None | None | None | N | None | 2.41441E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs1223583950 |
-0.623 | 0.111 | D | 0.604 | 0.354 | 0.467923293426 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.62E-05 | 0 | 0 |
| M/R | rs1223583950 |
-0.623 | 0.111 | D | 0.604 | 0.354 | 0.467923293426 | gnomAD-4.0.0 | 1.59059E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88168E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.638 | likely_pathogenic | 0.7655 | pathogenic | -2.06 | Highly Destabilizing | 0.006 | N | 0.485 | neutral | None | None | None | None | N |
| M/C | 0.8884 | likely_pathogenic | 0.9239 | pathogenic | -1.484 | Destabilizing | 0.54 | D | 0.675 | neutral | None | None | None | None | N |
| M/D | 0.972 | likely_pathogenic | 0.9823 | pathogenic | -0.438 | Destabilizing | 0.142 | N | 0.643 | neutral | None | None | None | None | N |
| M/E | 0.7785 | likely_pathogenic | 0.8538 | pathogenic | -0.322 | Destabilizing | 0.064 | N | 0.569 | neutral | None | None | None | None | N |
| M/F | 0.4653 | ambiguous | 0.4867 | ambiguous | -0.828 | Destabilizing | 0.064 | N | 0.462 | neutral | None | None | None | None | N |
| M/G | 0.8679 | likely_pathogenic | 0.9125 | pathogenic | -2.468 | Highly Destabilizing | 0.064 | N | 0.561 | neutral | None | None | None | None | N |
| M/H | 0.8031 | likely_pathogenic | 0.868 | pathogenic | -1.614 | Destabilizing | 0.781 | D | 0.687 | prob.neutral | None | None | None | None | N |
| M/I | 0.2483 | likely_benign | 0.4004 | ambiguous | -0.949 | Destabilizing | None | N | 0.101 | neutral | N | 0.411838702 | None | None | N |
| M/K | 0.4133 | ambiguous | 0.5542 | ambiguous | -0.613 | Destabilizing | 0.049 | N | 0.547 | neutral | D | 0.547388823 | None | None | N |
| M/L | 0.1496 | likely_benign | 0.1715 | benign | -0.949 | Destabilizing | 0.002 | N | 0.206 | neutral | N | 0.494689041 | None | None | N |
| M/N | 0.7715 | likely_pathogenic | 0.859 | pathogenic | -0.614 | Destabilizing | 0.142 | N | 0.624 | neutral | None | None | None | None | N |
| M/P | 0.9187 | likely_pathogenic | 0.9241 | pathogenic | -1.294 | Destabilizing | 0.251 | N | 0.628 | neutral | None | None | None | None | N |
| M/Q | 0.4637 | ambiguous | 0.56 | ambiguous | -0.513 | Destabilizing | 0.251 | N | 0.525 | neutral | None | None | None | None | N |
| M/R | 0.466 | ambiguous | 0.5943 | pathogenic | -0.434 | Destabilizing | 0.111 | N | 0.604 | neutral | D | 0.548054477 | None | None | N |
| M/S | 0.7023 | likely_pathogenic | 0.8079 | pathogenic | -1.363 | Destabilizing | 0.015 | N | 0.479 | neutral | None | None | None | None | N |
| M/T | 0.3954 | ambiguous | 0.5798 | pathogenic | -1.109 | Destabilizing | None | N | 0.283 | neutral | N | 0.487708222 | None | None | N |
| M/V | 0.0983 | likely_benign | 0.1457 | benign | -1.294 | Destabilizing | None | N | 0.1 | neutral | N | 0.459921314 | None | None | N |
| M/W | 0.8181 | likely_pathogenic | 0.853 | pathogenic | -0.812 | Destabilizing | 0.781 | D | 0.649 | neutral | None | None | None | None | N |
| M/Y | 0.7549 | likely_pathogenic | 0.7967 | pathogenic | -0.847 | Destabilizing | 0.251 | N | 0.616 | neutral | 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.