Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31104 | 93535;93536;93537 | chr2:178548316;178548315;178548314 | chr2:179413043;179413042;179413041 |
| N2AB | 29463 | 88612;88613;88614 | chr2:178548316;178548315;178548314 | chr2:179413043;179413042;179413041 |
| N2A | 28536 | 85831;85832;85833 | chr2:178548316;178548315;178548314 | chr2:179413043;179413042;179413041 |
| N2B | 22039 | 66340;66341;66342 | chr2:178548316;178548315;178548314 | chr2:179413043;179413042;179413041 |
| Novex-1 | 22164 | 66715;66716;66717 | chr2:178548316;178548315;178548314 | chr2:179413043;179413042;179413041 |
| Novex-2 | 22231 | 66916;66917;66918 | chr2:178548316;178548315;178548314 | chr2:179413043;179413042;179413041 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs745736147  |
-0.421 | 0.146 | N | 0.423 | 0.074 | 0.317958651998 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs745736147 |
-0.421 | 0.146 | N | 0.423 | 0.074 | 0.317958651998 | gnomAD-4.0.0 | 1.59116E-06 | None | None | None | None | N | None | 0 | 2.28634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs772169998 |
-1.657 | 0.002 | N | 0.436 | 0.251 | 0.52133269049 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 2.98864E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs772169998 |
-1.657 | 0.002 | N | 0.436 | 0.251 | 0.52133269049 | gnomAD-4.0.0 | 7.95553E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.43007E-04 | 0 | None | 0 | 0 | 5.71589E-06 | 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 | 0.5089 | ambiguous | 0.5826 | pathogenic | -2.043 | Highly Destabilizing | 0.09 | N | 0.464 | neutral | None | None | None | None | N |
| M/C | 0.7368 | likely_pathogenic | 0.8031 | pathogenic | -2.043 | Highly Destabilizing | 0.96 | D | 0.475 | neutral | None | None | None | None | N |
| M/D | 0.9322 | likely_pathogenic | 0.9461 | pathogenic | -2.041 | Highly Destabilizing | 0.524 | D | 0.651 | prob.neutral | None | None | None | None | N |
| M/E | 0.7954 | likely_pathogenic | 0.8232 | pathogenic | -1.824 | Destabilizing | 0.524 | D | 0.55 | neutral | None | None | None | None | N |
| M/F | 0.5345 | ambiguous | 0.5616 | ambiguous | -0.764 | Destabilizing | 0.524 | D | 0.514 | neutral | None | None | None | None | N |
| M/G | 0.7483 | likely_pathogenic | 0.8036 | pathogenic | -2.47 | Highly Destabilizing | 0.524 | D | 0.524 | neutral | None | None | None | None | N |
| M/H | 0.7829 | likely_pathogenic | 0.8085 | pathogenic | -2.046 | Highly Destabilizing | 0.96 | D | 0.535 | neutral | None | None | None | None | N |
| M/I | 0.3471 | ambiguous | 0.382 | ambiguous | -0.817 | Destabilizing | 0.146 | N | 0.423 | neutral | N | 0.38294844 | None | None | N |
| M/K | 0.5799 | likely_pathogenic | 0.6174 | pathogenic | -1.417 | Destabilizing | 0.454 | N | 0.537 | neutral | N | 0.458947709 | None | None | N |
| M/L | 0.1297 | likely_benign | 0.1563 | benign | -0.817 | Destabilizing | None | N | 0.192 | neutral | N | 0.392183999 | None | None | N |
| M/N | 0.5999 | likely_pathogenic | 0.6336 | pathogenic | -1.782 | Destabilizing | 0.524 | D | 0.563 | neutral | None | None | None | None | N |
| M/P | 0.9499 | likely_pathogenic | 0.941 | pathogenic | -1.21 | Destabilizing | 0.691 | D | 0.557 | neutral | None | None | None | None | N |
| M/Q | 0.5325 | ambiguous | 0.5675 | pathogenic | -1.537 | Destabilizing | 0.691 | D | 0.491 | neutral | None | None | None | None | N |
| M/R | 0.6409 | likely_pathogenic | 0.6821 | pathogenic | -1.377 | Destabilizing | 0.627 | D | 0.59 | neutral | N | 0.45877435 | None | None | N |
| M/S | 0.5038 | ambiguous | 0.5474 | ambiguous | -2.275 | Highly Destabilizing | 0.185 | N | 0.468 | neutral | None | None | None | None | N |
| M/T | 0.2381 | likely_benign | 0.2974 | benign | -1.949 | Destabilizing | 0.002 | N | 0.436 | neutral | N | 0.268644287 | None | None | N |
| M/V | 0.1491 | likely_benign | 0.1778 | benign | -1.21 | Destabilizing | 0.07 | N | 0.449 | neutral | N | 0.377926622 | None | None | N |
| M/W | 0.8631 | likely_pathogenic | 0.8574 | pathogenic | -1.095 | Destabilizing | 0.989 | D | 0.483 | neutral | None | None | None | None | N |
| M/Y | 0.7641 | likely_pathogenic | 0.769 | pathogenic | -1.023 | Destabilizing | 0.887 | D | 0.569 | 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.