Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15913 | 47962;47963;47964 | chr2:178617348;178617347;178617346 | chr2:179482075;179482074;179482073 |
| N2AB | 14272 | 43039;43040;43041 | chr2:178617348;178617347;178617346 | chr2:179482075;179482074;179482073 |
| N2A | 13345 | 40258;40259;40260 | chr2:178617348;178617347;178617346 | chr2:179482075;179482074;179482073 |
| N2B | 6848 | 20767;20768;20769 | chr2:178617348;178617347;178617346 | chr2:179482075;179482074;179482073 |
| Novex-1 | 6973 | 21142;21143;21144 | chr2:178617348;178617347;178617346 | chr2:179482075;179482074;179482073 |
| Novex-2 | 7040 | 21343;21344;21345 | chr2:178617348;178617347;178617346 | chr2:179482075;179482074;179482073 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs138576504  |
-1.737 | 0.916 | D | 0.618 | 0.286 | None | gnomAD-2.1.1 | 6.57552E-04 | None | None | None | None | N | None | 6.95994E-03 | 1.07735E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs138576504 |
-1.737 | 0.916 | D | 0.618 | 0.286 | None | gnomAD-3.1.2 | 2.05431E-03 | None | None | None | None | N | None | 6.88306E-03 | 1.5746E-03 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.43541E-03 |
| L/F | rs138576504 |
-1.737 | 0.916 | D | 0.618 | 0.286 | None | 1000 genomes | 2.19649E-03 | None | None | None | None | N | None | 7.6E-03 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/F | rs138576504 |
-1.737 | 0.916 | D | 0.618 | 0.286 | None | gnomAD-4.0.0 | 3.59135E-04 | None | None | None | None | N | None | 6.82301E-03 | 7.21994E-04 | None | 0 | 0 | None | 0 | 1.67504E-04 | 2.56979E-06 | 0 | 4.0851E-04 |
| L/P | rs1439310142 |
None | 0.002 | N | 0.369 | 0.081 | 0.495372917472 | gnomAD-4.0.0 | 3.35425E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.92484E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2029 | likely_benign | 0.2174 | benign | -1.737 | Destabilizing | 0.25 | N | 0.546 | neutral | None | None | None | None | N |
| L/C | 0.5898 | likely_pathogenic | 0.5889 | pathogenic | -1.051 | Destabilizing | 0.982 | D | 0.641 | neutral | None | None | None | None | N |
| L/D | 0.7558 | likely_pathogenic | 0.75 | pathogenic | -1.302 | Destabilizing | 0.7 | D | 0.728 | prob.delet. | None | None | None | None | N |
| L/E | 0.4379 | ambiguous | 0.4707 | ambiguous | -1.275 | Destabilizing | 0.7 | D | 0.728 | prob.delet. | None | None | None | None | N |
| L/F | 0.2778 | likely_benign | 0.3105 | benign | -1.128 | Destabilizing | 0.916 | D | 0.618 | neutral | D | 0.547167918 | None | None | N |
| L/G | 0.5607 | ambiguous | 0.5651 | pathogenic | -2.076 | Highly Destabilizing | 0.7 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/H | 0.3779 | ambiguous | 0.369 | ambiguous | -1.279 | Destabilizing | 0.976 | D | 0.705 | prob.neutral | N | 0.515356814 | None | None | N |
| L/I | 0.1221 | likely_benign | 0.1435 | benign | -0.864 | Destabilizing | 0.504 | D | 0.529 | neutral | N | 0.477131097 | None | None | N |
| L/K | 0.2775 | likely_benign | 0.2919 | benign | -1.238 | Destabilizing | 0.7 | D | 0.686 | prob.neutral | None | None | None | None | N |
| L/M | 0.1427 | likely_benign | 0.1563 | benign | -0.693 | Destabilizing | 0.935 | D | 0.615 | neutral | None | None | None | None | N |
| L/N | 0.4008 | ambiguous | 0.4194 | ambiguous | -1.111 | Destabilizing | 0.826 | D | 0.73 | prob.delet. | None | None | None | None | N |
| L/P | 0.1368 | likely_benign | 0.1247 | benign | -1.125 | Destabilizing | 0.002 | N | 0.369 | neutral | N | 0.455732247 | None | None | N |
| L/Q | 0.2377 | likely_benign | 0.2392 | benign | -1.272 | Destabilizing | 0.826 | D | 0.701 | prob.neutral | None | None | None | None | N |
| L/R | 0.2261 | likely_benign | 0.2203 | benign | -0.641 | Destabilizing | 0.781 | D | 0.696 | prob.neutral | N | 0.455886665 | None | None | N |
| L/S | 0.4065 | ambiguous | 0.4183 | ambiguous | -1.724 | Destabilizing | 0.7 | D | 0.59 | neutral | None | None | None | None | N |
| L/T | 0.2168 | likely_benign | 0.2494 | benign | -1.587 | Destabilizing | 0.7 | D | 0.603 | neutral | None | None | None | None | N |
| L/V | 0.118 | likely_benign | 0.1347 | benign | -1.125 | Destabilizing | 0.334 | N | 0.497 | neutral | N | 0.481833778 | None | None | N |
| L/W | 0.4151 | ambiguous | 0.4123 | ambiguous | -1.233 | Destabilizing | 0.982 | D | 0.71 | prob.delet. | None | None | None | None | N |
| L/Y | 0.4501 | ambiguous | 0.4619 | ambiguous | -1.011 | Destabilizing | 0.935 | D | 0.669 | 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.