Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29571 | 88936;88937;88938 | chr2:178554636;178554635;178554634 | chr2:179419363;179419362;179419361 |
| N2AB | 27930 | 84013;84014;84015 | chr2:178554636;178554635;178554634 | chr2:179419363;179419362;179419361 |
| N2A | 27003 | 81232;81233;81234 | chr2:178554636;178554635;178554634 | chr2:179419363;179419362;179419361 |
| N2B | 20506 | 61741;61742;61743 | chr2:178554636;178554635;178554634 | chr2:179419363;179419362;179419361 |
| Novex-1 | 20631 | 62116;62117;62118 | chr2:178554636;178554635;178554634 | chr2:179419363;179419362;179419361 |
| Novex-2 | 20698 | 62317;62318;62319 | chr2:178554636;178554635;178554634 | chr2:179419363;179419362;179419361 |
| 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/L | None | None | 0.476 | N | 0.582 | 0.177 | 0.410071178582 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| V/M | rs1244032310  |
-1.004 | 0.978 | N | 0.755 | 0.422 | 0.607763699848 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14705E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs1244032310 |
-1.004 | 0.978 | N | 0.755 | 0.422 | 0.607763699848 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs1244032310 |
-1.004 | 0.978 | N | 0.755 | 0.422 | 0.607763699848 | gnomAD-4.0.0 | 6.57289E-06 | None | None | None | None | N | None | 2.41359E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.5741 | likely_pathogenic | 0.6253 | pathogenic | -2.345 | Highly Destabilizing | 0.928 | D | 0.631 | neutral | D | 0.536868904 | None | None | N |
| V/C | 0.937 | likely_pathogenic | 0.9386 | pathogenic | -1.922 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| V/D | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -3.337 | Highly Destabilizing | 0.997 | D | 0.887 | deleterious | None | None | None | None | N |
| V/E | 0.9946 | likely_pathogenic | 0.995 | pathogenic | -3.012 | Highly Destabilizing | 0.996 | D | 0.872 | deleterious | D | 0.537629373 | None | None | N |
| V/F | 0.8717 | likely_pathogenic | 0.8834 | pathogenic | -1.349 | Destabilizing | 0.983 | D | 0.832 | deleterious | None | None | None | None | N |
| V/G | 0.911 | likely_pathogenic | 0.9229 | pathogenic | -2.977 | Highly Destabilizing | 0.989 | D | 0.877 | deleterious | D | 0.537629373 | None | None | N |
| V/H | 0.9979 | likely_pathogenic | 0.998 | pathogenic | -2.93 | Highly Destabilizing | 0.999 | D | 0.881 | deleterious | None | None | None | None | N |
| V/I | 0.0878 | likely_benign | 0.0901 | benign | -0.512 | Destabilizing | 0.05 | N | 0.323 | neutral | None | None | None | None | N |
| V/K | 0.9955 | likely_pathogenic | 0.9956 | pathogenic | -1.981 | Destabilizing | 0.992 | D | 0.873 | deleterious | None | None | None | None | N |
| V/L | 0.4419 | ambiguous | 0.4757 | ambiguous | -0.512 | Destabilizing | 0.476 | N | 0.582 | neutral | N | 0.459500361 | None | None | N |
| V/M | 0.5891 | likely_pathogenic | 0.6193 | pathogenic | -0.784 | Destabilizing | 0.978 | D | 0.755 | deleterious | N | 0.507661833 | None | None | N |
| V/N | 0.9953 | likely_pathogenic | 0.9957 | pathogenic | -2.659 | Highly Destabilizing | 0.997 | D | 0.899 | deleterious | None | None | None | None | N |
| V/P | 0.9911 | likely_pathogenic | 0.9923 | pathogenic | -1.103 | Destabilizing | 0.997 | D | 0.884 | deleterious | None | None | None | None | N |
| V/Q | 0.9926 | likely_pathogenic | 0.993 | pathogenic | -2.292 | Highly Destabilizing | 0.997 | D | 0.908 | deleterious | None | None | None | None | N |
| V/R | 0.991 | likely_pathogenic | 0.9911 | pathogenic | -2.085 | Highly Destabilizing | 0.992 | D | 0.904 | deleterious | None | None | None | None | N |
| V/S | 0.945 | likely_pathogenic | 0.9547 | pathogenic | -3.21 | Highly Destabilizing | 0.992 | D | 0.874 | deleterious | None | None | None | None | N |
| V/T | 0.7061 | likely_pathogenic | 0.7466 | pathogenic | -2.717 | Highly Destabilizing | 0.944 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/W | 0.9976 | likely_pathogenic | 0.9979 | pathogenic | -1.963 | Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | N |
| V/Y | 0.9927 | likely_pathogenic | 0.9931 | pathogenic | -1.605 | Destabilizing | 0.992 | D | 0.837 | 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.