Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23451 | 70576;70577;70578 | chr2:178575781;178575780;178575779 | chr2:179440508;179440507;179440506 |
| N2AB | 21810 | 65653;65654;65655 | chr2:178575781;178575780;178575779 | chr2:179440508;179440507;179440506 |
| N2A | 20883 | 62872;62873;62874 | chr2:178575781;178575780;178575779 | chr2:179440508;179440507;179440506 |
| N2B | 14386 | 43381;43382;43383 | chr2:178575781;178575780;178575779 | chr2:179440508;179440507;179440506 |
| Novex-1 | 14511 | 43756;43757;43758 | chr2:178575781;178575780;178575779 | chr2:179440508;179440507;179440506 |
| Novex-2 | 14578 | 43957;43958;43959 | chr2:178575781;178575780;178575779 | chr2:179440508;179440507;179440506 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs754456949  |
None | 1.0 | N | 0.795 | 0.468 | 0.414670632993 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs754456949 |
None | 1.0 | N | 0.795 | 0.468 | 0.414670632993 | gnomAD-4.0.0 | 6.57834E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47124E-05 | 0 | 0 |
| S/T | rs1339742394 |
-0.85 | 0.065 | D | 0.359 | 0.168 | 0.156986980423 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/T | rs1339742394 |
-0.85 | 0.065 | D | 0.359 | 0.168 | 0.156986980423 | gnomAD-4.0.0 | 3.18474E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.8659E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1034 | likely_benign | 0.1101 | benign | -0.569 | Destabilizing | 0.966 | D | 0.497 | neutral | None | None | None | None | N |
| S/C | 0.1016 | likely_benign | 0.1071 | benign | -0.903 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.496436296 | None | None | N |
| S/D | 0.7336 | likely_pathogenic | 0.7412 | pathogenic | -1.629 | Destabilizing | 0.999 | D | 0.575 | neutral | None | None | None | None | N |
| S/E | 0.7457 | likely_pathogenic | 0.7498 | pathogenic | -1.586 | Destabilizing | 0.999 | D | 0.585 | neutral | None | None | None | None | N |
| S/F | 0.2205 | likely_benign | 0.2412 | benign | -0.914 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| S/G | 0.1538 | likely_benign | 0.157 | benign | -0.802 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.494181344 | None | None | N |
| S/H | 0.4282 | ambiguous | 0.4071 | ambiguous | -1.306 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| S/I | 0.3244 | likely_benign | 0.3663 | ambiguous | -0.051 | Destabilizing | 1.0 | D | 0.776 | deleterious | D | 0.543583038 | None | None | N |
| S/K | 0.8752 | likely_pathogenic | 0.881 | pathogenic | -0.679 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | N |
| S/L | 0.1641 | likely_benign | 0.1982 | benign | -0.051 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| S/M | 0.2029 | likely_benign | 0.2234 | benign | 0.143 | Stabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| S/N | 0.2674 | likely_benign | 0.2749 | benign | -1.052 | Destabilizing | 0.985 | D | 0.566 | neutral | N | 0.502157061 | None | None | N |
| S/P | 0.9907 | likely_pathogenic | 0.9932 | pathogenic | -0.192 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| S/Q | 0.6822 | likely_pathogenic | 0.6694 | pathogenic | -1.26 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/R | 0.8126 | likely_pathogenic | 0.8165 | pathogenic | -0.546 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.497877874 | None | None | N |
| S/T | 0.0898 | likely_benign | 0.0962 | benign | -0.836 | Destabilizing | 0.065 | N | 0.359 | neutral | D | 0.524450343 | None | None | N |
| S/V | 0.2985 | likely_benign | 0.3332 | benign | -0.192 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/W | 0.5114 | ambiguous | 0.5211 | ambiguous | -1.02 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| S/Y | 0.2438 | likely_benign | 0.2559 | benign | -0.626 | Destabilizing | 0.991 | D | 0.508 | 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.