Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21911 | 65956;65957;65958 | chr2:178583072;178583071;178583070 | chr2:179447799;179447798;179447797 |
| N2AB | 20270 | 61033;61034;61035 | chr2:178583072;178583071;178583070 | chr2:179447799;179447798;179447797 |
| N2A | 19343 | 58252;58253;58254 | chr2:178583072;178583071;178583070 | chr2:179447799;179447798;179447797 |
| N2B | 12846 | 38761;38762;38763 | chr2:178583072;178583071;178583070 | chr2:179447799;179447798;179447797 |
| Novex-1 | 12971 | 39136;39137;39138 | chr2:178583072;178583071;178583070 | chr2:179447799;179447798;179447797 |
| Novex-2 | 13038 | 39337;39338;39339 | chr2:178583072;178583071;178583070 | chr2:179447799;179447798;179447797 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs372565084  |
-0.37 | 0.999 | N | 0.559 | 0.415 | None | gnomAD-2.1.1 | 2.9E-05 | None | None | None | None | N | None | 3.34364E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/E | rs372565084 |
-0.37 | 0.999 | N | 0.559 | 0.415 | None | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | N | None | 3.13676E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs372565084 |
-0.37 | 0.999 | N | 0.559 | 0.415 | None | gnomAD-4.0.0 | 1.6135E-05 | None | None | None | None | N | None | 3.33992E-04 | 1.67274E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/N | rs1226949981 |
None | 1.0 | N | 0.691 | 0.372 | 0.282179105231 | gnomAD-4.0.0 | 1.11798E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.00759E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.5685 | likely_pathogenic | 0.5185 | ambiguous | -0.579 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| K/C | 0.7299 | likely_pathogenic | 0.7255 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| K/D | 0.8048 | likely_pathogenic | 0.7693 | pathogenic | 0.261 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| K/E | 0.3606 | ambiguous | 0.3135 | benign | 0.376 | Stabilizing | 0.999 | D | 0.559 | neutral | N | 0.486479106 | None | None | N |
| K/F | 0.8805 | likely_pathogenic | 0.861 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| K/G | 0.7093 | likely_pathogenic | 0.6692 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/H | 0.3148 | likely_benign | 0.3008 | benign | -1.066 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| K/I | 0.5081 | ambiguous | 0.4637 | ambiguous | 0.311 | Stabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| K/L | 0.5345 | ambiguous | 0.4918 | ambiguous | 0.311 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/M | 0.4064 | ambiguous | 0.3568 | ambiguous | 0.064 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.486950685 | None | None | N |
| K/N | 0.575 | likely_pathogenic | 0.5205 | ambiguous | -0.299 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.500216407 | None | None | N |
| K/P | 0.9547 | likely_pathogenic | 0.9393 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| K/Q | 0.1658 | likely_benign | 0.148 | benign | -0.333 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.474800674 | None | None | N |
| K/R | 0.0837 | likely_benign | 0.0818 | benign | -0.36 | Destabilizing | 0.999 | D | 0.522 | neutral | N | 0.440514742 | None | None | N |
| K/S | 0.5556 | ambiguous | 0.5008 | ambiguous | -1.026 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| K/T | 0.2489 | likely_benign | 0.2087 | benign | -0.698 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.47701426 | None | None | N |
| K/V | 0.4636 | ambiguous | 0.4203 | ambiguous | 0.044 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| K/W | 0.8673 | likely_pathogenic | 0.8481 | pathogenic | -0.137 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7837 | likely_pathogenic | 0.7531 | pathogenic | 0.14 | Stabilizing | 1.0 | D | 0.731 | 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.