Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3101 | 9526;9527;9528 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
| N2AB | 3101 | 9526;9527;9528 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
| N2A | 3101 | 9526;9527;9528 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
| N2B | 3055 | 9388;9389;9390 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
| Novex-1 | 3055 | 9388;9389;9390 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
| Novex-2 | 3055 | 9388;9389;9390 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
| Novex-3 | 3101 | 9526;9527;9528 | chr2:178768018;178768017;178768016 | chr2:179632745;179632744;179632743 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs148676491  |
0.098 | 0.003 | N | 0.2 | 0.07 | 0.0716867268079 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.64E-05 | 0 |
| D/E | rs148676491 |
0.098 | 0.003 | N | 0.2 | 0.07 | 0.0716867268079 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/E | rs148676491 |
0.098 | 0.003 | N | 0.2 | 0.07 | 0.0716867268079 | gnomAD-4.0.0 | 1.48698E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56143E-05 | 0 | 1.77964E-05 | 0 | 3.20092E-05 |
| D/N | None | None | 0.722 | N | 0.373 | 0.231 | 0.101711395817 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3853 | ambiguous | 0.4057 | ambiguous | 0.062 | Stabilizing | 0.722 | D | 0.395 | neutral | N | 0.345494775 | None | None | N |
| D/C | 0.9039 | likely_pathogenic | 0.9182 | pathogenic | -0.083 | Destabilizing | 0.996 | D | 0.569 | neutral | None | None | None | None | N |
| D/E | 0.1883 | likely_benign | 0.1694 | benign | -0.29 | Destabilizing | 0.003 | N | 0.2 | neutral | N | 0.348618714 | None | None | N |
| D/F | 0.9186 | likely_pathogenic | 0.9343 | pathogenic | -0.061 | Destabilizing | 0.858 | D | 0.513 | neutral | None | None | None | None | N |
| D/G | 0.266 | likely_benign | 0.2872 | benign | -0.046 | Destabilizing | 0.722 | D | 0.347 | neutral | N | 0.340157885 | None | None | N |
| D/H | 0.5694 | likely_pathogenic | 0.6198 | pathogenic | 0.504 | Stabilizing | 0.901 | D | 0.373 | neutral | N | 0.36258107 | None | None | N |
| D/I | 0.8348 | likely_pathogenic | 0.8648 | pathogenic | 0.274 | Stabilizing | 0.923 | D | 0.515 | neutral | None | None | None | None | N |
| D/K | 0.6189 | likely_pathogenic | 0.6615 | pathogenic | 0.462 | Stabilizing | 0.633 | D | 0.373 | neutral | None | None | None | None | N |
| D/L | 0.781 | likely_pathogenic | 0.8179 | pathogenic | 0.274 | Stabilizing | 0.858 | D | 0.449 | neutral | None | None | None | None | N |
| D/M | 0.9004 | likely_pathogenic | 0.9119 | pathogenic | 0.085 | Stabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | N |
| D/N | 0.1642 | likely_benign | 0.1767 | benign | 0.26 | Stabilizing | 0.722 | D | 0.373 | neutral | N | 0.334544537 | None | None | N |
| D/P | 0.7086 | likely_pathogenic | 0.7016 | pathogenic | 0.222 | Stabilizing | 0.961 | D | 0.372 | neutral | None | None | None | None | N |
| D/Q | 0.5619 | ambiguous | 0.5874 | pathogenic | 0.254 | Stabilizing | 0.858 | D | 0.335 | neutral | None | None | None | None | N |
| D/R | 0.6887 | likely_pathogenic | 0.7323 | pathogenic | 0.659 | Stabilizing | 0.923 | D | 0.46 | neutral | None | None | None | None | N |
| D/S | 0.195 | likely_benign | 0.2118 | benign | 0.162 | Stabilizing | 0.775 | D | 0.333 | neutral | None | None | None | None | N |
| D/T | 0.5323 | ambiguous | 0.5597 | ambiguous | 0.25 | Stabilizing | 0.775 | D | 0.362 | neutral | None | None | None | None | N |
| D/V | 0.6358 | likely_pathogenic | 0.6905 | pathogenic | 0.222 | Stabilizing | 0.901 | D | 0.458 | neutral | N | 0.392253952 | None | None | N |
| D/W | 0.972 | likely_pathogenic | 0.9783 | pathogenic | -0.037 | Destabilizing | 0.989 | D | 0.561 | neutral | None | None | None | None | N |
| D/Y | 0.6236 | likely_pathogenic | 0.7009 | pathogenic | 0.161 | Stabilizing | 0.018 | N | 0.433 | neutral | N | 0.406852537 | 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.