Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2594 | 8005;8006;8007 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
| N2AB | 2594 | 8005;8006;8007 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
| N2A | 2594 | 8005;8006;8007 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
| N2B | 2548 | 7867;7868;7869 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
| Novex-1 | 2548 | 7867;7868;7869 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
| Novex-2 | 2548 | 7867;7868;7869 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
| Novex-3 | 2594 | 8005;8006;8007 | chr2:178773184;178773183;178773182 | chr2:179637911;179637910;179637909 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs764016233  |
-1.758 | 0.01 | N | 0.37 | 0.355 | 0.623315389809 | gnomAD-2.1.1 | 7.99E-06 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs764016233 |
-1.758 | 0.01 | N | 0.37 | 0.355 | 0.623315389809 | gnomAD-4.0.0 | 2.05273E-06 | None | None | None | None | N | None | 0 | 4.47768E-05 | None | 0 | 0 | None | 0 | 0 | 8.99415E-07 | 0 | 0 |
| M/V | rs913684550 |
None | 0.028 | N | 0.19 | 0.226 | 0.497741790239 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs913684550 |
None | 0.028 | N | 0.19 | 0.226 | 0.497741790239 | gnomAD-4.0.0 | 3.09849E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23773E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5089 | ambiguous | 0.5478 | ambiguous | -1.651 | Destabilizing | 0.013 | N | 0.355 | neutral | None | None | None | None | N |
| M/C | 0.7882 | likely_pathogenic | 0.7859 | pathogenic | -1.842 | Destabilizing | 0.993 | D | 0.641 | neutral | None | None | None | None | N |
| M/D | 0.9895 | likely_pathogenic | 0.9882 | pathogenic | -2.311 | Highly Destabilizing | 0.932 | D | 0.653 | neutral | None | None | None | None | N |
| M/E | 0.9301 | likely_pathogenic | 0.9214 | pathogenic | -2.239 | Highly Destabilizing | 0.932 | D | 0.567 | neutral | None | None | None | None | N |
| M/F | 0.8671 | likely_pathogenic | 0.8577 | pathogenic | -0.872 | Destabilizing | 0.932 | D | 0.584 | neutral | None | None | None | None | N |
| M/G | 0.8988 | likely_pathogenic | 0.8992 | pathogenic | -1.963 | Destabilizing | 0.584 | D | 0.531 | neutral | None | None | None | None | N |
| M/H | 0.9567 | likely_pathogenic | 0.948 | pathogenic | -1.491 | Destabilizing | 0.993 | D | 0.663 | neutral | None | None | None | None | N |
| M/I | 0.6992 | likely_pathogenic | 0.7205 | pathogenic | -0.814 | Destabilizing | 0.514 | D | 0.361 | neutral | N | 0.409595773 | None | None | N |
| M/K | 0.7928 | likely_pathogenic | 0.7659 | pathogenic | -1.078 | Destabilizing | 0.679 | D | 0.526 | neutral | N | 0.506132055 | None | None | N |
| M/L | 0.2715 | likely_benign | 0.272 | benign | -0.814 | Destabilizing | 0.166 | N | 0.335 | neutral | N | 0.427457292 | None | None | N |
| M/N | 0.9055 | likely_pathogenic | 0.9015 | pathogenic | -1.246 | Destabilizing | 0.932 | D | 0.633 | neutral | None | None | None | None | N |
| M/P | 0.9628 | likely_pathogenic | 0.9678 | pathogenic | -1.072 | Destabilizing | 0.932 | D | 0.62 | neutral | None | None | None | None | N |
| M/Q | 0.7384 | likely_pathogenic | 0.7314 | pathogenic | -1.286 | Destabilizing | 0.977 | D | 0.584 | neutral | None | None | None | None | N |
| M/R | 0.7905 | likely_pathogenic | 0.7624 | pathogenic | -0.832 | Destabilizing | 0.912 | D | 0.589 | neutral | N | 0.506132055 | None | None | N |
| M/S | 0.7412 | likely_pathogenic | 0.7446 | pathogenic | -1.61 | Destabilizing | 0.584 | D | 0.461 | neutral | None | None | None | None | N |
| M/T | 0.3525 | ambiguous | 0.3869 | ambiguous | -1.443 | Destabilizing | 0.01 | N | 0.37 | neutral | N | 0.421365379 | None | None | N |
| M/V | 0.1446 | likely_benign | 0.1568 | benign | -1.072 | Destabilizing | 0.028 | N | 0.19 | neutral | N | 0.348931919 | None | None | N |
| M/W | 0.9856 | likely_pathogenic | 0.9809 | pathogenic | -1.109 | Destabilizing | 0.998 | D | 0.608 | neutral | None | None | None | None | N |
| M/Y | 0.9668 | likely_pathogenic | 0.9587 | pathogenic | -0.982 | Destabilizing | 0.993 | D | 0.67 | 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.