Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1143 | 3652;3653;3654 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
| N2AB | 1143 | 3652;3653;3654 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
| N2A | 1143 | 3652;3653;3654 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
| N2B | 1097 | 3514;3515;3516 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
| Novex-1 | 1097 | 3514;3515;3516 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
| Novex-2 | 1097 | 3514;3515;3516 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
| Novex-3 | 1143 | 3652;3653;3654 | chr2:178781217;178781216;178781215 | chr2:179645944;179645943;179645942 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1466464278  |
-1.184 | 0.993 | D | 0.422 | 0.562 | 0.703432857381 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| I/L | rs1466464278 |
-1.184 | 0.993 | D | 0.422 | 0.562 | 0.703432857381 | gnomAD-4.0.0 | 1.59077E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8568E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9932 | likely_pathogenic | 0.9914 | pathogenic | -2.911 | Highly Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/C | 0.9942 | likely_pathogenic | 0.9916 | pathogenic | -2.394 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| I/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.447 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| I/E | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -3.13 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| I/F | 0.8823 | likely_pathogenic | 0.835 | pathogenic | -1.781 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.59461885 | None | None | N |
| I/G | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -3.545 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| I/H | 0.9988 | likely_pathogenic | 0.9985 | pathogenic | -3.173 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| I/K | 0.9978 | likely_pathogenic | 0.9977 | pathogenic | -2.276 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| I/L | 0.5834 | likely_pathogenic | 0.5092 | ambiguous | -1.02 | Destabilizing | 0.993 | D | 0.422 | neutral | D | 0.529405022 | None | None | N |
| I/M | 0.6852 | likely_pathogenic | 0.5991 | pathogenic | -1.236 | Destabilizing | 1.0 | D | 0.775 | deleterious | D | 0.653317963 | None | None | N |
| I/N | 0.9961 | likely_pathogenic | 0.9957 | pathogenic | -2.925 | Highly Destabilizing | 1.0 | D | 0.92 | deleterious | D | 0.732582044 | None | None | N |
| I/P | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.639 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| I/Q | 0.9984 | likely_pathogenic | 0.9982 | pathogenic | -2.601 | Highly Destabilizing | 1.0 | D | 0.927 | deleterious | None | None | None | None | N |
| I/R | 0.9966 | likely_pathogenic | 0.9964 | pathogenic | -2.231 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| I/S | 0.9951 | likely_pathogenic | 0.9946 | pathogenic | -3.603 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.769665219 | None | None | N |
| I/T | 0.9938 | likely_pathogenic | 0.9928 | pathogenic | -3.111 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.695907722 | None | None | N |
| I/V | 0.3156 | likely_benign | 0.2726 | benign | -1.639 | Destabilizing | 0.993 | D | 0.387 | neutral | D | 0.548074507 | None | None | N |
| I/W | 0.9988 | likely_pathogenic | 0.9983 | pathogenic | -2.19 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| I/Y | 0.992 | likely_pathogenic | 0.9904 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.849 | 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.