Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23533 | 70822;70823;70824 | chr2:178575535;178575534;178575533 | chr2:179440262;179440261;179440260 |
| N2AB | 21892 | 65899;65900;65901 | chr2:178575535;178575534;178575533 | chr2:179440262;179440261;179440260 |
| N2A | 20965 | 63118;63119;63120 | chr2:178575535;178575534;178575533 | chr2:179440262;179440261;179440260 |
| N2B | 14468 | 43627;43628;43629 | chr2:178575535;178575534;178575533 | chr2:179440262;179440261;179440260 |
| Novex-1 | 14593 | 44002;44003;44004 | chr2:178575535;178575534;178575533 | chr2:179440262;179440261;179440260 |
| Novex-2 | 14660 | 44203;44204;44205 | chr2:178575535;178575534;178575533 | chr2:179440262;179440261;179440260 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs886055250  |
-1.49 | 0.978 | D | 0.675 | 0.437 | 0.390220360785 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| P/A | rs886055250 |
-1.49 | 0.978 | D | 0.675 | 0.437 | 0.390220360785 | gnomAD-4.0.0 | 1.59148E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85902E-06 | 0 | 0 |
| P/Q | rs747427532 |
-2.086 | 0.999 | D | 0.877 | 0.518 | 0.494031935134 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 1.29232E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/Q | rs747427532 |
-2.086 | 0.999 | D | 0.877 | 0.518 | 0.494031935134 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/Q | rs747427532 |
-2.086 | 0.999 | D | 0.877 | 0.518 | 0.494031935134 | gnomAD-4.0.0 | 3.84413E-06 | None | None | None | None | N | None | 5.07597E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs886055250 |
None | 0.999 | D | 0.822 | 0.483 | 0.427940940899 | gnomAD-4.0.0 | 1.59148E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02425E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8762 | likely_pathogenic | 0.9308 | pathogenic | -1.411 | Destabilizing | 0.978 | D | 0.675 | prob.neutral | D | 0.535011436 | None | None | N |
| P/C | 0.993 | likely_pathogenic | 0.9958 | pathogenic | -1.968 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| P/D | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -3.101 | Highly Destabilizing | 0.992 | D | 0.875 | deleterious | None | None | None | None | N |
| P/E | 0.9989 | likely_pathogenic | 0.9992 | pathogenic | -3.059 | Highly Destabilizing | 0.985 | D | 0.843 | deleterious | None | None | None | None | N |
| P/F | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -1.186 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| P/G | 0.9957 | likely_pathogenic | 0.9976 | pathogenic | -1.707 | Destabilizing | 0.999 | D | 0.836 | deleterious | None | None | None | None | N |
| P/H | 0.9986 | likely_pathogenic | 0.9991 | pathogenic | -1.158 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| P/I | 0.9875 | likely_pathogenic | 0.9906 | pathogenic | -0.665 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| P/K | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -1.395 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| P/L | 0.9677 | likely_pathogenic | 0.9784 | pathogenic | -0.665 | Destabilizing | 0.945 | D | 0.638 | neutral | D | 0.533743989 | None | None | N |
| P/M | 0.9963 | likely_pathogenic | 0.9973 | pathogenic | -0.903 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| P/N | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -1.682 | Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | N |
| P/Q | 0.9978 | likely_pathogenic | 0.9985 | pathogenic | -1.891 | Destabilizing | 0.999 | D | 0.877 | deleterious | D | 0.55387616 | None | None | N |
| P/R | 0.9962 | likely_pathogenic | 0.9973 | pathogenic | -0.906 | Destabilizing | 0.999 | D | 0.861 | deleterious | D | 0.542266365 | None | None | N |
| P/S | 0.9889 | likely_pathogenic | 0.9941 | pathogenic | -2.008 | Highly Destabilizing | 0.999 | D | 0.822 | deleterious | D | 0.535264926 | None | None | N |
| P/T | 0.987 | likely_pathogenic | 0.9919 | pathogenic | -1.866 | Destabilizing | 0.996 | D | 0.827 | deleterious | N | 0.504727955 | None | None | N |
| P/V | 0.9624 | likely_pathogenic | 0.9739 | pathogenic | -0.886 | Destabilizing | 0.999 | D | 0.81 | deleterious | None | None | None | None | N |
| P/W | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -1.478 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| P/Y | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -1.107 | Destabilizing | 1.0 | D | 0.881 | deleterious | 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.