Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14072 | 42439;42440;42441 | chr2:178634567;178634566;178634565 | chr2:179499294;179499293;179499292 |
| N2AB | 12431 | 37516;37517;37518 | chr2:178634567;178634566;178634565 | chr2:179499294;179499293;179499292 |
| N2A | 11504 | 34735;34736;34737 | chr2:178634567;178634566;178634565 | chr2:179499294;179499293;179499292 |
| N2B | 5007 | 15244;15245;15246 | chr2:178634567;178634566;178634565 | chr2:179499294;179499293;179499292 |
| Novex-1 | 5132 | 15619;15620;15621 | chr2:178634567;178634566;178634565 | chr2:179499294;179499293;179499292 |
| Novex-2 | 5199 | 15820;15821;15822 | chr2:178634567;178634566;178634565 | chr2:179499294;179499293;179499292 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs747161377  |
0.366 | 0.858 | N | 0.508 | 0.296 | 0.221019684889 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/L | rs747161377 |
0.366 | 0.858 | N | 0.508 | 0.296 | 0.221019684889 | gnomAD-4.0.0 | 1.02659E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04439E-05 | None | 0 | 0 | 1.16955E-05 | 0 | 0 |
| R/P | rs747161377 |
None | 0.998 | N | 0.587 | 0.321 | 0.364342057095 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/P | rs747161377 |
None | 0.998 | N | 0.587 | 0.321 | 0.364342057095 | gnomAD-4.0.0 | 6.84396E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99654E-07 | 0 | 0 |
| R/Q | None | -0.106 | 0.985 | N | 0.578 | 0.254 | 0.188950314367 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11707E-04 | None | 6.54E-05 | None | 0 | 8.91E-06 | 0 |
| R/Q | None | -0.106 | 0.985 | N | 0.578 | 0.254 | 0.188950314367 | gnomAD-4.0.0 | 1.30035E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.5222E-05 | None | 1.8728E-05 | 0 | 7.19723E-06 | 9.27924E-05 | 1.65717E-05 |
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 | 0.7939 | likely_pathogenic | 0.7722 | pathogenic | -0.42 | Destabilizing | 0.863 | D | 0.536 | neutral | None | None | None | None | N |
| R/C | 0.3629 | ambiguous | 0.3602 | ambiguous | -0.583 | Destabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| R/D | 0.9467 | likely_pathogenic | 0.9406 | pathogenic | 0.022 | Stabilizing | 0.969 | D | 0.589 | neutral | None | None | None | None | N |
| R/E | 0.7136 | likely_pathogenic | 0.6944 | pathogenic | 0.153 | Stabilizing | 0.939 | D | 0.588 | neutral | None | None | None | None | N |
| R/F | 0.8177 | likely_pathogenic | 0.795 | pathogenic | -0.277 | Destabilizing | 0.991 | D | 0.609 | neutral | None | None | None | None | N |
| R/G | 0.7795 | likely_pathogenic | 0.7735 | pathogenic | -0.714 | Destabilizing | 0.983 | D | 0.546 | neutral | N | 0.467554926 | None | None | N |
| R/H | 0.1927 | likely_benign | 0.1963 | benign | -1.043 | Destabilizing | 0.997 | D | 0.576 | neutral | None | None | None | None | N |
| R/I | 0.4514 | ambiguous | 0.4278 | ambiguous | 0.356 | Stabilizing | 0.17 | N | 0.468 | neutral | None | None | None | None | N |
| R/K | 0.2319 | likely_benign | 0.2102 | benign | -0.433 | Destabilizing | 0.079 | N | 0.292 | neutral | None | None | None | None | N |
| R/L | 0.4937 | ambiguous | 0.4526 | ambiguous | 0.356 | Stabilizing | 0.858 | D | 0.508 | neutral | N | 0.447263948 | None | None | N |
| R/M | 0.5827 | likely_pathogenic | 0.5517 | ambiguous | -0.209 | Destabilizing | 0.991 | D | 0.574 | neutral | None | None | None | None | N |
| R/N | 0.8776 | likely_pathogenic | 0.8632 | pathogenic | -0.201 | Destabilizing | 0.969 | D | 0.555 | neutral | None | None | None | None | N |
| R/P | 0.9783 | likely_pathogenic | 0.979 | pathogenic | 0.119 | Stabilizing | 0.998 | D | 0.587 | neutral | N | 0.506440456 | None | None | N |
| R/Q | 0.2178 | likely_benign | 0.2128 | benign | -0.245 | Destabilizing | 0.985 | D | 0.578 | neutral | N | 0.439873971 | None | None | N |
| R/S | 0.8122 | likely_pathogenic | 0.7944 | pathogenic | -0.795 | Destabilizing | 0.939 | D | 0.563 | neutral | None | None | None | None | N |
| R/T | 0.5336 | ambiguous | 0.5026 | ambiguous | -0.482 | Destabilizing | 0.969 | D | 0.541 | neutral | None | None | None | None | N |
| R/V | 0.5418 | ambiguous | 0.5138 | ambiguous | 0.119 | Stabilizing | 0.884 | D | 0.534 | neutral | None | None | None | None | N |
| R/W | 0.394 | ambiguous | 0.4034 | ambiguous | -0.087 | Destabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | N |
| R/Y | 0.6521 | likely_pathogenic | 0.6402 | pathogenic | 0.24 | Stabilizing | 0.997 | D | 0.593 | 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.