Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6023 | 18292;18293;18294 | chr2:178730333;178730332;178730331 | chr2:179595060;179595059;179595058 |
| N2AB | 5706 | 17341;17342;17343 | chr2:178730333;178730332;178730331 | chr2:179595060;179595059;179595058 |
| N2A | 4779 | 14560;14561;14562 | chr2:178730333;178730332;178730331 | chr2:179595060;179595059;179595058 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1037108046  |
-1.575 | 0.76 | N | 0.442 | 0.374 | 0.549249573952 | gnomAD-2.1.1 | 7.33E-06 | None | None | None | None | N | None | 4.18E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.05E-06 | 0 |
| V/A | rs1037108046 |
-1.575 | 0.76 | N | 0.442 | 0.374 | 0.549249573952 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/A | rs1037108046 |
-1.575 | 0.76 | N | 0.442 | 0.374 | 0.549249573952 | gnomAD-4.0.0 | 2.23812E-05 | None | None | None | None | N | None | 1.3369E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71902E-05 | 0 | 4.81943E-05 |
| V/F | rs2080216835 |
None | 0.991 | D | 0.667 | 0.637 | 0.864907916677 | gnomAD-4.0.0 | 6.86678E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01869E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2246 | likely_benign | 0.1845 | benign | -1.931 | Destabilizing | 0.76 | D | 0.442 | neutral | N | 0.504432935 | None | None | N |
| V/C | 0.7986 | likely_pathogenic | 0.7438 | pathogenic | -1.423 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| V/D | 0.6926 | likely_pathogenic | 0.6286 | pathogenic | -2.418 | Highly Destabilizing | 0.982 | D | 0.689 | prob.neutral | D | 0.554032696 | None | None | N |
| V/E | 0.6027 | likely_pathogenic | 0.5407 | ambiguous | -2.336 | Highly Destabilizing | 0.986 | D | 0.664 | neutral | None | None | None | None | N |
| V/F | 0.3341 | likely_benign | 0.2962 | benign | -1.333 | Destabilizing | 0.991 | D | 0.667 | neutral | D | 0.530395033 | None | None | N |
| V/G | 0.3511 | ambiguous | 0.2962 | benign | -2.337 | Highly Destabilizing | 0.982 | D | 0.696 | prob.neutral | N | 0.521431811 | None | None | N |
| V/H | 0.8529 | likely_pathogenic | 0.8099 | pathogenic | -2.004 | Highly Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/I | 0.0834 | likely_benign | 0.085 | benign | -0.859 | Destabilizing | 0.863 | D | 0.497 | neutral | N | 0.495561967 | None | None | N |
| V/K | 0.6819 | likely_pathogenic | 0.6174 | pathogenic | -1.683 | Destabilizing | 0.986 | D | 0.663 | neutral | None | None | None | None | N |
| V/L | 0.352 | ambiguous | 0.3322 | benign | -0.859 | Destabilizing | 0.76 | D | 0.471 | neutral | N | 0.491651627 | None | None | N |
| V/M | 0.2179 | likely_benign | 0.2052 | benign | -0.731 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/N | 0.5693 | likely_pathogenic | 0.5336 | ambiguous | -1.667 | Destabilizing | 0.986 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/P | 0.9549 | likely_pathogenic | 0.9351 | pathogenic | -1.185 | Destabilizing | 0.993 | D | 0.661 | neutral | None | None | None | None | N |
| V/Q | 0.6417 | likely_pathogenic | 0.5765 | pathogenic | -1.74 | Destabilizing | 0.993 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/R | 0.6337 | likely_pathogenic | 0.5582 | ambiguous | -1.244 | Destabilizing | 0.993 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/S | 0.3533 | ambiguous | 0.298 | benign | -2.188 | Highly Destabilizing | 0.973 | D | 0.641 | neutral | None | None | None | None | N |
| V/T | 0.1996 | likely_benign | 0.19 | benign | -1.996 | Destabilizing | 0.214 | N | 0.32 | neutral | None | None | None | None | N |
| V/W | 0.9375 | likely_pathogenic | 0.909 | pathogenic | -1.712 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| V/Y | 0.7987 | likely_pathogenic | 0.7454 | pathogenic | -1.399 | Destabilizing | 0.998 | D | 0.663 | 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.