Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26969 | 81130;81131;81132 | chr2:178565227;178565226;178565225 | chr2:179429954;179429953;179429952 |
| N2AB | 25328 | 76207;76208;76209 | chr2:178565227;178565226;178565225 | chr2:179429954;179429953;179429952 |
| N2A | 24401 | 73426;73427;73428 | chr2:178565227;178565226;178565225 | chr2:179429954;179429953;179429952 |
| N2B | 17904 | 53935;53936;53937 | chr2:178565227;178565226;178565225 | chr2:179429954;179429953;179429952 |
| Novex-1 | 18029 | 54310;54311;54312 | chr2:178565227;178565226;178565225 | chr2:179429954;179429953;179429952 |
| Novex-2 | 18096 | 54511;54512;54513 | chr2:178565227;178565226;178565225 | chr2:179429954;179429953;179429952 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs377667066  |
-0.073 | 0.002 | N | 0.401 | 0.126 | None | gnomAD-2.1.1 | 6.44E-05 | None | None | None | None | I | None | 8.27E-05 | 5.66E-05 | None | 0 | 5.14E-05 | None | 9.81E-05 | None | 0 | 6.27E-05 | 2.81136E-04 |
| V/I | rs377667066 |
-0.073 | 0.002 | N | 0.401 | 0.126 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 3.87297E-04 | None | 0 | 0 | 4.41E-05 | 2.07211E-04 | 0 |
| V/I | rs377667066 |
-0.073 | 0.002 | N | 0.401 | 0.126 | None | gnomAD-4.0.0 | 4.9584E-05 | None | None | None | None | I | None | 2.67115E-05 | 3.33611E-05 | None | 0 | 4.4619E-05 | None | 0 | 0 | 5.50989E-05 | 6.58863E-05 | 4.804E-05 |
| V/L | None | None | 0.022 | D | 0.593 | 0.364 | 0.511848488485 | gnomAD-4.0.0 | 6.84288E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99531E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7451 | likely_pathogenic | 0.6988 | pathogenic | -1.626 | Destabilizing | 0.104 | N | 0.649 | neutral | D | 0.630126568 | None | None | I |
| V/C | 0.9239 | likely_pathogenic | 0.9021 | pathogenic | -1.082 | Destabilizing | 0.968 | D | 0.704 | prob.neutral | None | None | None | None | I |
| V/D | 0.9911 | likely_pathogenic | 0.9859 | pathogenic | -1.364 | Destabilizing | 0.667 | D | 0.715 | prob.delet. | D | 0.630731981 | None | None | I |
| V/E | 0.9815 | likely_pathogenic | 0.9761 | pathogenic | -1.275 | Destabilizing | 0.726 | D | 0.67 | neutral | None | None | None | None | I |
| V/F | 0.5931 | likely_pathogenic | 0.5314 | ambiguous | -1.038 | Destabilizing | 0.715 | D | 0.694 | prob.neutral | D | 0.630126568 | None | None | I |
| V/G | 0.8823 | likely_pathogenic | 0.8621 | pathogenic | -2.031 | Highly Destabilizing | 0.667 | D | 0.71 | prob.delet. | D | 0.630731981 | None | None | I |
| V/H | 0.9873 | likely_pathogenic | 0.9805 | pathogenic | -1.619 | Destabilizing | 0.968 | D | 0.727 | prob.delet. | None | None | None | None | I |
| V/I | 0.0821 | likely_benign | 0.0711 | benign | -0.571 | Destabilizing | 0.002 | N | 0.401 | neutral | N | 0.512906064 | None | None | I |
| V/K | 0.983 | likely_pathogenic | 0.9779 | pathogenic | -1.186 | Destabilizing | 0.726 | D | 0.672 | neutral | None | None | None | None | I |
| V/L | 0.4543 | ambiguous | 0.3743 | ambiguous | -0.571 | Destabilizing | 0.022 | N | 0.593 | neutral | D | 0.590730016 | None | None | I |
| V/M | 0.5005 | ambiguous | 0.416 | ambiguous | -0.525 | Destabilizing | 0.567 | D | 0.688 | prob.neutral | None | None | None | None | I |
| V/N | 0.9458 | likely_pathogenic | 0.9112 | pathogenic | -1.12 | Destabilizing | 0.89 | D | 0.712 | prob.delet. | None | None | None | None | I |
| V/P | 0.9423 | likely_pathogenic | 0.9299 | pathogenic | -0.89 | Destabilizing | 0.89 | D | 0.672 | neutral | None | None | None | None | I |
| V/Q | 0.9723 | likely_pathogenic | 0.9609 | pathogenic | -1.157 | Destabilizing | 0.89 | D | 0.677 | prob.neutral | None | None | None | None | I |
| V/R | 0.9694 | likely_pathogenic | 0.9625 | pathogenic | -0.871 | Destabilizing | 0.726 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/S | 0.85 | likely_pathogenic | 0.8066 | pathogenic | -1.766 | Destabilizing | 0.726 | D | 0.655 | neutral | None | None | None | None | I |
| V/T | 0.6903 | likely_pathogenic | 0.6243 | pathogenic | -1.557 | Destabilizing | 0.272 | N | 0.681 | prob.neutral | None | None | None | None | I |
| V/W | 0.9908 | likely_pathogenic | 0.9866 | pathogenic | -1.337 | Destabilizing | 0.968 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/Y | 0.9579 | likely_pathogenic | 0.9376 | pathogenic | -0.998 | Destabilizing | 0.726 | D | 0.697 | prob.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.