Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14060 | 42403;42404;42405 | chr2:178634603;178634602;178634601 | chr2:179499330;179499329;179499328 |
| N2AB | 12419 | 37480;37481;37482 | chr2:178634603;178634602;178634601 | chr2:179499330;179499329;179499328 |
| N2A | 11492 | 34699;34700;34701 | chr2:178634603;178634602;178634601 | chr2:179499330;179499329;179499328 |
| N2B | 4995 | 15208;15209;15210 | chr2:178634603;178634602;178634601 | chr2:179499330;179499329;179499328 |
| Novex-1 | 5120 | 15583;15584;15585 | chr2:178634603;178634602;178634601 | chr2:179499330;179499329;179499328 |
| Novex-2 | 5187 | 15784;15785;15786 | chr2:178634603;178634602;178634601 | chr2:179499330;179499329;179499328 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | None | None | 1.0 | N | 0.915 | 0.491 | 0.694961532487 | gnomAD-4.0.0 | 1.5923E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.027E-05 |
| L/V | rs762418323  |
-1.25 | 0.999 | D | 0.493 | 0.312 | 0.31411915649 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| L/V | rs762418323 |
-1.25 | 0.999 | D | 0.493 | 0.312 | 0.31411915649 | gnomAD-4.0.0 | 6.36914E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14409E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9539 | likely_pathogenic | 0.9575 | pathogenic | -2.225 | Highly Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/C | 0.9722 | likely_pathogenic | 0.9719 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -1.933 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| L/E | 0.9931 | likely_pathogenic | 0.9937 | pathogenic | -1.738 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| L/F | 0.9128 | likely_pathogenic | 0.9149 | pathogenic | -1.244 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| L/G | 0.9921 | likely_pathogenic | 0.9927 | pathogenic | -2.753 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/H | 0.9949 | likely_pathogenic | 0.9952 | pathogenic | -2.102 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| L/I | 0.4974 | ambiguous | 0.4941 | ambiguous | -0.726 | Destabilizing | 0.999 | D | 0.507 | neutral | None | None | None | None | N |
| L/K | 0.9925 | likely_pathogenic | 0.9916 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| L/M | 0.5617 | ambiguous | 0.5432 | ambiguous | -0.697 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | N | 0.449182294 | None | None | N |
| L/N | 0.9957 | likely_pathogenic | 0.9952 | pathogenic | -1.647 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| L/P | 0.9652 | likely_pathogenic | 0.9737 | pathogenic | -1.203 | Destabilizing | 1.0 | D | 0.915 | deleterious | N | 0.431640192 | None | None | N |
| L/Q | 0.9835 | likely_pathogenic | 0.9818 | pathogenic | -1.546 | Destabilizing | 1.0 | D | 0.905 | deleterious | D | 0.67560494 | None | None | N |
| L/R | 0.9864 | likely_pathogenic | 0.9862 | pathogenic | -1.216 | Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.67560494 | None | None | N |
| L/S | 0.9933 | likely_pathogenic | 0.9933 | pathogenic | -2.435 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| L/T | 0.9778 | likely_pathogenic | 0.975 | pathogenic | -2.092 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| L/V | 0.5648 | likely_pathogenic | 0.5663 | pathogenic | -1.203 | Destabilizing | 0.999 | D | 0.493 | neutral | D | 0.612612227 | None | None | N |
| L/W | 0.9913 | likely_pathogenic | 0.9925 | pathogenic | -1.538 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| L/Y | 0.9959 | likely_pathogenic | 0.996 | pathogenic | -1.245 | Destabilizing | 1.0 | D | 0.869 | 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.