Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14014 | 42265;42266;42267 | chr2:178634834;178634833;178634832 | chr2:179499561;179499560;179499559 |
| N2AB | 12373 | 37342;37343;37344 | chr2:178634834;178634833;178634832 | chr2:179499561;179499560;179499559 |
| N2A | 11446 | 34561;34562;34563 | chr2:178634834;178634833;178634832 | chr2:179499561;179499560;179499559 |
| N2B | 4949 | 15070;15071;15072 | chr2:178634834;178634833;178634832 | chr2:179499561;179499560;179499559 |
| Novex-1 | 5074 | 15445;15446;15447 | chr2:178634834;178634833;178634832 | chr2:179499561;179499560;179499559 |
| Novex-2 | 5141 | 15646;15647;15648 | chr2:178634834;178634833;178634832 | chr2:179499561;179499560;179499559 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs1200308695  |
-0.761 | 0.03 | N | 0.37 | 0.084 | 0.149567049428 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.41E-05 | None | 0 | 0 | 0 |
| A/E | rs1200308695 |
-0.761 | 0.03 | N | 0.37 | 0.084 | 0.149567049428 | gnomAD-4.0.0 | 1.60109E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4576E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6498 | likely_pathogenic | 0.5625 | ambiguous | -0.813 | Destabilizing | 0.685 | D | 0.337 | neutral | None | None | None | None | N |
| A/D | 0.4526 | ambiguous | 0.3573 | ambiguous | -0.38 | Destabilizing | 0.221 | N | 0.502 | neutral | None | None | None | None | N |
| A/E | 0.2021 | likely_benign | 0.2331 | benign | -0.471 | Destabilizing | 0.03 | N | 0.37 | neutral | N | 0.432195296 | None | None | N |
| A/F | 0.4568 | ambiguous | 0.3808 | ambiguous | -0.756 | Destabilizing | 0.221 | N | 0.523 | neutral | None | None | None | None | N |
| A/G | 0.221 | likely_benign | 0.1685 | benign | -0.636 | Destabilizing | 0.058 | N | 0.323 | neutral | N | 0.42563932 | None | None | N |
| A/H | 0.616 | likely_pathogenic | 0.556 | ambiguous | -0.649 | Destabilizing | 0.518 | D | 0.451 | neutral | None | None | None | None | N |
| A/I | 0.359 | ambiguous | 0.2911 | benign | -0.229 | Destabilizing | 0.039 | N | 0.363 | neutral | None | None | None | None | N |
| A/K | 0.6531 | likely_pathogenic | 0.5992 | pathogenic | -0.829 | Destabilizing | 0.039 | N | 0.376 | neutral | None | None | None | None | N |
| A/L | 0.2733 | likely_benign | 0.2134 | benign | -0.229 | Destabilizing | None | N | 0.281 | neutral | None | None | None | None | N |
| A/M | 0.2132 | likely_benign | 0.19 | benign | -0.356 | Destabilizing | 0.016 | N | 0.337 | neutral | None | None | None | None | N |
| A/N | 0.3238 | likely_benign | 0.254 | benign | -0.544 | Destabilizing | 0.221 | N | 0.504 | neutral | None | None | None | None | N |
| A/P | 0.8055 | likely_pathogenic | 0.6198 | pathogenic | -0.272 | Destabilizing | 0.303 | N | 0.384 | neutral | N | 0.42509198 | None | None | N |
| A/Q | 0.2303 | likely_benign | 0.3078 | benign | -0.729 | Destabilizing | 0.001 | N | 0.393 | neutral | None | None | None | None | N |
| A/R | 0.6173 | likely_pathogenic | 0.5471 | ambiguous | -0.439 | Destabilizing | 0.125 | N | 0.386 | neutral | None | None | None | None | N |
| A/S | 0.0994 | likely_benign | 0.0883 | benign | -0.86 | Destabilizing | 0.002 | N | 0.244 | neutral | N | 0.426469299 | None | None | N |
| A/T | 0.1194 | likely_benign | 0.0995 | benign | -0.852 | Destabilizing | None | N | 0.247 | neutral | N | 0.433613584 | None | None | N |
| A/V | 0.1917 | likely_benign | 0.1486 | benign | -0.272 | Destabilizing | 0.03 | N | 0.32 | neutral | N | 0.430634681 | None | None | N |
| A/W | 0.8386 | likely_pathogenic | 0.7683 | pathogenic | -0.98 | Destabilizing | 0.869 | D | 0.636 | neutral | None | None | None | None | N |
| A/Y | 0.611 | likely_pathogenic | 0.5189 | ambiguous | -0.604 | Destabilizing | 0.366 | N | 0.481 | 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.