Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31786 | 95581;95582;95583 | chr2:178545880;178545879;178545878 | chr2:179410607;179410606;179410605 |
| N2AB | 30145 | 90658;90659;90660 | chr2:178545880;178545879;178545878 | chr2:179410607;179410606;179410605 |
| N2A | 29218 | 87877;87878;87879 | chr2:178545880;178545879;178545878 | chr2:179410607;179410606;179410605 |
| N2B | 22721 | 68386;68387;68388 | chr2:178545880;178545879;178545878 | chr2:179410607;179410606;179410605 |
| Novex-1 | 22846 | 68761;68762;68763 | chr2:178545880;178545879;178545878 | chr2:179410607;179410606;179410605 |
| Novex-2 | 22913 | 68962;68963;68964 | chr2:178545880;178545879;178545878 | chr2:179410607;179410606;179410605 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs869320743  |
-0.663 | 1.0 | D | 0.737 | 0.842 | 0.32471235697 |
Pfeffer (2013)
Palmio (2019)
| None |
HMERF 
|
het | None | None | N | Genetic analysis of genes in 127 undiagnosed patients, likely MFM; co-segregates with condition (n = 2, 2 affected (total 7)) | None | None | None | None | None | None | None | None | None | None | None |
| N/K | rs869320743 |
-0.663 | 1.0 | D | 0.737 | 0.842 | 0.32471235697 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| N/S | rs1696865626 |
None | 0.999 | N | 0.58 | 0.623 | 0.317958651998 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9954 | likely_pathogenic | 0.9937 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| N/C | 0.9268 | likely_pathogenic | 0.9077 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| N/D | 0.9866 | likely_pathogenic | 0.9871 | pathogenic | -2.145 | Highly Destabilizing | 0.999 | D | 0.598 | neutral | D | 0.527650695 | None | None | N |
| N/E | 0.9982 | likely_pathogenic | 0.9977 | pathogenic | -1.944 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| N/F | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| N/G | 0.978 | likely_pathogenic | 0.9696 | pathogenic | -1.351 | Destabilizing | 0.999 | D | 0.555 | neutral | None | None | None | None | N |
| N/H | 0.9773 | likely_pathogenic | 0.9737 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.556643956 | None | None | N |
| N/I | 0.9963 | likely_pathogenic | 0.9956 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.557150935 | None | None | N |
| N/K | 0.9985 | likely_pathogenic | 0.9984 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.549135538 | None | None | N |
| N/L | 0.9806 | likely_pathogenic | 0.9772 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| N/M | 0.9944 | likely_pathogenic | 0.9933 | pathogenic | 0.1 | Stabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| N/P | 0.9974 | likely_pathogenic | 0.9968 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| N/Q | 0.9975 | likely_pathogenic | 0.9968 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| N/R | 0.9968 | likely_pathogenic | 0.9964 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| N/S | 0.7233 | likely_pathogenic | 0.687 | pathogenic | -1.211 | Destabilizing | 0.999 | D | 0.58 | neutral | N | 0.517874097 | None | None | N |
| N/T | 0.931 | likely_pathogenic | 0.9363 | pathogenic | -0.846 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | N | 0.508222404 | None | None | N |
| N/V | 0.9929 | likely_pathogenic | 0.9913 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| N/W | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| N/Y | 0.9955 | likely_pathogenic | 0.9947 | pathogenic | -0.338 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.568253751 | 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.