Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1132 | 3619;3620;3621 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
| N2AB | 1132 | 3619;3620;3621 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
| N2A | 1132 | 3619;3620;3621 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
| N2B | 1086 | 3481;3482;3483 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
| Novex-1 | 1086 | 3481;3482;3483 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
| Novex-2 | 1086 | 3481;3482;3483 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
| Novex-3 | 1132 | 3619;3620;3621 | chr2:178781250;178781249;178781248 | chr2:179645977;179645976;179645975 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1433964543  |
None | 0.993 | D | 0.804 | 0.54 | 0.595016529804 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs1433964543 |
None | 0.993 | D | 0.804 | 0.54 | 0.595016529804 | 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 |
| Y/C | rs1433964543 |
None | 0.993 | D | 0.804 | 0.54 | 0.595016529804 | gnomAD-4.0.0 | 2.56158E-06 | None | None | None | None | N | None | 3.38112E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/F | None | None | 0.645 | N | 0.643 | 0.321 | 0.33835085245 | gnomAD-4.0.0 | 1.59099E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85722E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8942 | likely_pathogenic | 0.881 | pathogenic | -2.292 | Highly Destabilizing | 0.707 | D | 0.747 | deleterious | None | None | None | None | N |
| Y/C | 0.3605 | ambiguous | 0.3233 | benign | -1.025 | Destabilizing | 0.993 | D | 0.804 | deleterious | D | 0.549810519 | None | None | N |
| Y/D | 0.9232 | likely_pathogenic | 0.9136 | pathogenic | -0.751 | Destabilizing | 0.864 | D | 0.816 | deleterious | N | 0.503952697 | None | None | N |
| Y/E | 0.9536 | likely_pathogenic | 0.9482 | pathogenic | -0.666 | Destabilizing | 0.809 | D | 0.777 | deleterious | None | None | None | None | N |
| Y/F | 0.1771 | likely_benign | 0.1521 | benign | -1.052 | Destabilizing | 0.645 | D | 0.643 | neutral | N | 0.49779072 | None | None | N |
| Y/G | 0.8802 | likely_pathogenic | 0.8766 | pathogenic | -2.617 | Highly Destabilizing | 0.894 | D | 0.8 | deleterious | None | None | None | None | N |
| Y/H | 0.411 | ambiguous | 0.3747 | ambiguous | -1.079 | Destabilizing | 0.006 | N | 0.379 | neutral | N | 0.512741498 | None | None | N |
| Y/I | 0.824 | likely_pathogenic | 0.7909 | pathogenic | -1.31 | Destabilizing | 0.945 | D | 0.802 | deleterious | None | None | None | None | N |
| Y/K | 0.9597 | likely_pathogenic | 0.9517 | pathogenic | -1.111 | Destabilizing | 0.894 | D | 0.802 | deleterious | None | None | None | None | N |
| Y/L | 0.7548 | likely_pathogenic | 0.7305 | pathogenic | -1.31 | Destabilizing | 0.707 | D | 0.722 | prob.delet. | None | None | None | None | N |
| Y/M | 0.8911 | likely_pathogenic | 0.8761 | pathogenic | -0.968 | Destabilizing | 0.995 | D | 0.78 | deleterious | None | None | None | None | N |
| Y/N | 0.6653 | likely_pathogenic | 0.639 | pathogenic | -1.387 | Destabilizing | 0.761 | D | 0.801 | deleterious | N | 0.497435619 | None | None | N |
| Y/P | 0.9904 | likely_pathogenic | 0.9905 | pathogenic | -1.632 | Destabilizing | 0.945 | D | 0.832 | deleterious | None | None | None | None | N |
| Y/Q | 0.8848 | likely_pathogenic | 0.8691 | pathogenic | -1.324 | Destabilizing | 0.894 | D | 0.796 | deleterious | None | None | None | None | N |
| Y/R | 0.8716 | likely_pathogenic | 0.8512 | pathogenic | -0.679 | Destabilizing | 0.894 | D | 0.818 | deleterious | None | None | None | None | N |
| Y/S | 0.6543 | likely_pathogenic | 0.6334 | pathogenic | -1.983 | Destabilizing | 0.864 | D | 0.776 | deleterious | N | 0.460837066 | None | None | N |
| Y/T | 0.8482 | likely_pathogenic | 0.8365 | pathogenic | -1.799 | Destabilizing | 0.945 | D | 0.811 | deleterious | None | None | None | None | N |
| Y/V | 0.7069 | likely_pathogenic | 0.6757 | pathogenic | -1.632 | Destabilizing | 0.945 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/W | 0.4918 | ambiguous | 0.459 | ambiguous | -0.656 | Destabilizing | 0.995 | D | 0.723 | prob.delet. | 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.