Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3224 | 9895;9896;9897 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
| N2AB | 3224 | 9895;9896;9897 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
| N2A | 3224 | 9895;9896;9897 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
| N2B | 3178 | 9757;9758;9759 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
| Novex-1 | 3178 | 9757;9758;9759 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
| Novex-2 | 3178 | 9757;9758;9759 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
| Novex-3 | 3224 | 9895;9896;9897 | chr2:178766414;178766413;178766412 | chr2:179631141;179631140;179631139 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs557221911  |
-0.323 | 0.549 | N | 0.489 | 0.184 | 0.231873229951 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | I | None | 0 | 8.68E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| R/G | rs557221911 |
-0.323 | 0.549 | N | 0.489 | 0.184 | 0.231873229951 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 1.30924E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs557221911 |
-0.323 | 0.549 | N | 0.489 | 0.184 | 0.231873229951 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/G | rs557221911 |
-0.323 | 0.549 | N | 0.489 | 0.184 | 0.231873229951 | gnomAD-4.0.0 | 3.71726E-06 | None | None | None | None | I | None | 0 | 8.33139E-05 | None | 0 | 0 | None | 0 | 0 | 8.47502E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7792 | likely_pathogenic | 0.7463 | pathogenic | -0.038 | Destabilizing | 0.25 | N | 0.409 | neutral | None | None | None | None | I |
| R/C | 0.6447 | likely_pathogenic | 0.5802 | pathogenic | -0.302 | Destabilizing | 0.992 | D | 0.48 | neutral | None | None | None | None | I |
| R/D | 0.9071 | likely_pathogenic | 0.8847 | pathogenic | -0.346 | Destabilizing | 0.617 | D | 0.508 | neutral | None | None | None | None | I |
| R/E | 0.6996 | likely_pathogenic | 0.6653 | pathogenic | -0.323 | Destabilizing | 0.25 | N | 0.374 | neutral | None | None | None | None | I |
| R/F | 0.9024 | likely_pathogenic | 0.8964 | pathogenic | -0.396 | Destabilizing | 0.972 | D | 0.465 | neutral | None | None | None | None | I |
| R/G | 0.5455 | ambiguous | 0.4958 | ambiguous | -0.143 | Destabilizing | 0.549 | D | 0.489 | neutral | N | 0.349700269 | None | None | I |
| R/H | 0.2932 | likely_benign | 0.2581 | benign | -0.602 | Destabilizing | 0.92 | D | 0.395 | neutral | None | None | None | None | I |
| R/I | 0.6809 | likely_pathogenic | 0.6908 | pathogenic | 0.189 | Stabilizing | 0.92 | D | 0.471 | neutral | None | None | None | None | I |
| R/K | 0.1257 | likely_benign | 0.1254 | benign | -0.245 | Destabilizing | 0.001 | N | 0.323 | neutral | N | 0.339528911 | None | None | I |
| R/L | 0.6468 | likely_pathogenic | 0.6353 | pathogenic | 0.189 | Stabilizing | 0.617 | D | 0.489 | neutral | None | None | None | None | I |
| R/M | 0.6542 | likely_pathogenic | 0.6588 | pathogenic | -0.159 | Destabilizing | 0.963 | D | 0.436 | neutral | N | 0.32422556 | None | None | I |
| R/N | 0.8051 | likely_pathogenic | 0.7831 | pathogenic | -0.138 | Destabilizing | 0.617 | D | 0.399 | neutral | None | None | None | None | I |
| R/P | 0.8566 | likely_pathogenic | 0.8146 | pathogenic | 0.129 | Stabilizing | 0.92 | D | 0.491 | neutral | None | None | None | None | I |
| R/Q | 0.2132 | likely_benign | 0.2004 | benign | -0.178 | Destabilizing | 0.447 | N | 0.422 | neutral | None | None | None | None | I |
| R/S | 0.8037 | likely_pathogenic | 0.7752 | pathogenic | -0.296 | Destabilizing | 0.379 | N | 0.446 | neutral | N | 0.345671811 | None | None | I |
| R/T | 0.6633 | likely_pathogenic | 0.6377 | pathogenic | -0.186 | Destabilizing | 0.549 | D | 0.455 | neutral | N | 0.34214336 | None | None | I |
| R/V | 0.7686 | likely_pathogenic | 0.7556 | pathogenic | 0.129 | Stabilizing | 0.85 | D | 0.52 | neutral | None | None | None | None | I |
| R/W | 0.5252 | ambiguous | 0.5176 | ambiguous | -0.603 | Destabilizing | 0.99 | D | 0.508 | neutral | N | 0.324887318 | None | None | I |
| R/Y | 0.8093 | likely_pathogenic | 0.7857 | pathogenic | -0.219 | Destabilizing | 0.972 | D | 0.465 | 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.