Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33256 | 99991;99992;99993 | chr2:178537441;178537440;178537439 | chr2:179402168;179402167;179402166 |
| N2AB | 31615 | 95068;95069;95070 | chr2:178537441;178537440;178537439 | chr2:179402168;179402167;179402166 |
| N2A | 30688 | 92287;92288;92289 | chr2:178537441;178537440;178537439 | chr2:179402168;179402167;179402166 |
| N2B | 24191 | 72796;72797;72798 | chr2:178537441;178537440;178537439 | chr2:179402168;179402167;179402166 |
| Novex-1 | 24316 | 73171;73172;73173 | chr2:178537441;178537440;178537439 | chr2:179402168;179402167;179402166 |
| Novex-2 | 24383 | 73372;73373;73374 | chr2:178537441;178537440;178537439 | chr2:179402168;179402167;179402166 |
| 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 | rs752102823  |
-1.18 | None | N | 0.271 | 0.117 | 0.282575091529 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 1.45994E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs752102823 |
-1.18 | None | N | 0.271 | 0.117 | 0.282575091529 | gnomAD-4.0.0 | 7.96686E-06 | None | None | None | None | N | None | 0 | 1.14574E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs755612464 |
-1.181 | None | N | 0.257 | 0.264 | 0.34854441366 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.51E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/L | rs755612464 |
-1.181 | None | N | 0.257 | 0.264 | 0.34854441366 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs755612464 |
-1.181 | None | N | 0.257 | 0.264 | 0.34854441366 | gnomAD-4.0.0 | 6.57004E-06 | None | None | None | None | N | None | 2.41243E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.8908 | likely_pathogenic | 0.9239 | pathogenic | -2.818 | Highly Destabilizing | 0.151 | N | 0.497 | neutral | None | None | None | None | N |
| M/C | 0.8893 | likely_pathogenic | 0.9049 | pathogenic | -2.723 | Highly Destabilizing | 0.98 | D | 0.714 | prob.delet. | None | None | None | None | N |
| M/D | 0.9979 | likely_pathogenic | 0.9984 | pathogenic | -2.544 | Highly Destabilizing | 0.977 | D | 0.735 | prob.delet. | None | None | None | None | N |
| M/E | 0.9776 | likely_pathogenic | 0.9833 | pathogenic | -2.312 | Highly Destabilizing | 0.945 | D | 0.704 | prob.neutral | None | None | None | None | N |
| M/F | 0.5016 | ambiguous | 0.5105 | ambiguous | -1.16 | Destabilizing | 0.021 | N | 0.561 | neutral | None | None | None | None | N |
| M/G | 0.9811 | likely_pathogenic | 0.9856 | pathogenic | -3.312 | Highly Destabilizing | 0.983 | D | 0.707 | prob.neutral | None | None | None | None | N |
| M/H | 0.975 | likely_pathogenic | 0.9834 | pathogenic | -2.803 | Highly Destabilizing | 0.953 | D | 0.759 | deleterious | None | None | None | None | N |
| M/I | 0.2287 | likely_benign | 0.3213 | benign | -1.384 | Destabilizing | None | N | 0.271 | neutral | N | 0.266988061 | None | None | N |
| M/K | 0.9232 | likely_pathogenic | 0.9535 | pathogenic | -1.983 | Destabilizing | 0.891 | D | 0.637 | neutral | N | 0.431703258 | None | None | N |
| M/L | 0.1505 | likely_benign | 0.1682 | benign | -1.384 | Destabilizing | None | N | 0.257 | neutral | N | 0.346177642 | None | None | N |
| M/N | 0.9801 | likely_pathogenic | 0.9876 | pathogenic | -2.342 | Highly Destabilizing | 0.992 | D | 0.713 | prob.delet. | None | None | None | None | N |
| M/P | 0.9978 | likely_pathogenic | 0.9981 | pathogenic | -1.847 | Destabilizing | 0.992 | D | 0.703 | prob.neutral | None | None | None | None | N |
| M/Q | 0.9092 | likely_pathogenic | 0.9307 | pathogenic | -2.046 | Highly Destabilizing | 0.994 | D | 0.599 | neutral | None | None | None | None | N |
| M/R | 0.9342 | likely_pathogenic | 0.9554 | pathogenic | -1.926 | Destabilizing | 0.977 | D | 0.641 | neutral | N | 0.431703258 | None | None | N |
| M/S | 0.9528 | likely_pathogenic | 0.9699 | pathogenic | -2.936 | Highly Destabilizing | 0.983 | D | 0.619 | neutral | None | None | None | None | N |
| M/T | 0.844 | likely_pathogenic | 0.9104 | pathogenic | -2.578 | Highly Destabilizing | 0.085 | N | 0.593 | neutral | N | 0.431356541 | None | None | N |
| M/V | 0.1252 | likely_benign | 0.1667 | benign | -1.847 | Destabilizing | 0.001 | N | 0.273 | neutral | N | 0.328111957 | None | None | N |
| M/W | 0.9346 | likely_pathogenic | 0.9469 | pathogenic | -1.469 | Destabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | N |
| M/Y | 0.9197 | likely_pathogenic | 0.9374 | pathogenic | -1.543 | Destabilizing | 0.72 | D | 0.649 | 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.