Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16334 | 49225;49226;49227 | chr2:178614514;178614513;178614512 | chr2:179479241;179479240;179479239 |
| N2AB | 14693 | 44302;44303;44304 | chr2:178614514;178614513;178614512 | chr2:179479241;179479240;179479239 |
| N2A | 13766 | 41521;41522;41523 | chr2:178614514;178614513;178614512 | chr2:179479241;179479240;179479239 |
| N2B | 7269 | 22030;22031;22032 | chr2:178614514;178614513;178614512 | chr2:179479241;179479240;179479239 |
| Novex-1 | 7394 | 22405;22406;22407 | chr2:178614514;178614513;178614512 | chr2:179479241;179479240;179479239 |
| Novex-2 | 7461 | 22606;22607;22608 | chr2:178614514;178614513;178614512 | chr2:179479241;179479240;179479239 |
| 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/A | None | None | 0.201 | N | 0.412 | 0.199 | 0.446310458034 | gnomAD-4.0.0 | 1.59507E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43653E-05 | 0 |
| V/M | rs541384076  |
-0.417 | 0.036 | D | 0.272 | 0.256 | 0.432379865206 | gnomAD-2.1.1 | 7.68E-05 | None | None | None | None | I | None | 0 | 2.03737E-04 | None | 0 | 0 | None | 3.28774E-04 | None | 0 | 0 | 3.33778E-04 |
| V/M | rs541384076 |
-0.417 | 0.036 | D | 0.272 | 0.256 | 0.432379865206 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14766E-04 | 0 |
| V/M | rs541384076 |
-0.417 | 0.036 | D | 0.272 | 0.256 | 0.432379865206 | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| V/M | rs541384076 |
-0.417 | 0.036 | D | 0.272 | 0.256 | 0.432379865206 | gnomAD-4.0.0 | 2.66757E-05 | None | None | None | None | I | None | 0 | 1.50296E-04 | None | 0 | 0 | None | 0 | 0 | 8.48247E-07 | 3.08126E-04 | 8.01462E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3039 | likely_benign | 0.2717 | benign | -1.26 | Destabilizing | 0.201 | N | 0.412 | neutral | N | 0.497587622 | None | None | I |
| V/C | 0.8121 | likely_pathogenic | 0.7837 | pathogenic | -0.811 | Destabilizing | 0.992 | D | 0.461 | neutral | None | None | None | None | I |
| V/D | 0.6849 | likely_pathogenic | 0.6434 | pathogenic | -1.406 | Destabilizing | 0.92 | D | 0.575 | neutral | None | None | None | None | I |
| V/E | 0.3955 | ambiguous | 0.3637 | ambiguous | -1.485 | Destabilizing | 0.896 | D | 0.541 | neutral | N | 0.490237311 | None | None | I |
| V/F | 0.3345 | likely_benign | 0.3205 | benign | -1.293 | Destabilizing | 0.85 | D | 0.469 | neutral | None | None | None | None | I |
| V/G | 0.4678 | ambiguous | 0.4369 | ambiguous | -1.486 | Destabilizing | 0.712 | D | 0.558 | neutral | D | 0.527399943 | None | None | I |
| V/H | 0.732 | likely_pathogenic | 0.7011 | pathogenic | -1.096 | Destabilizing | 0.992 | D | 0.577 | neutral | None | None | None | None | I |
| V/I | 0.0923 | likely_benign | 0.092 | benign | -0.768 | Destabilizing | 0.25 | N | 0.415 | neutral | None | None | None | None | I |
| V/K | 0.468 | ambiguous | 0.4273 | ambiguous | -1.046 | Destabilizing | 0.617 | D | 0.539 | neutral | None | None | None | None | I |
| V/L | 0.3349 | likely_benign | 0.3121 | benign | -0.768 | Destabilizing | 0.08 | N | 0.385 | neutral | D | 0.530238119 | None | None | I |
| V/M | 0.1909 | likely_benign | 0.1812 | benign | -0.456 | Destabilizing | 0.036 | N | 0.272 | neutral | D | 0.594411788 | None | None | I |
| V/N | 0.4158 | ambiguous | 0.4048 | ambiguous | -0.738 | Destabilizing | 0.92 | D | 0.585 | neutral | None | None | None | None | I |
| V/P | 0.9865 | likely_pathogenic | 0.9836 | pathogenic | -0.898 | Destabilizing | 0.972 | D | 0.572 | neutral | None | None | None | None | I |
| V/Q | 0.391 | ambiguous | 0.3587 | ambiguous | -1.044 | Destabilizing | 0.92 | D | 0.586 | neutral | None | None | None | None | I |
| V/R | 0.4851 | ambiguous | 0.4349 | ambiguous | -0.433 | Destabilizing | 0.85 | D | 0.593 | neutral | None | None | None | None | I |
| V/S | 0.304 | likely_benign | 0.2849 | benign | -1.117 | Destabilizing | 0.447 | N | 0.555 | neutral | None | None | None | None | I |
| V/T | 0.1827 | likely_benign | 0.1753 | benign | -1.106 | Destabilizing | 0.009 | N | 0.135 | neutral | None | None | None | None | I |
| V/W | 0.9376 | likely_pathogenic | 0.9293 | pathogenic | -1.403 | Destabilizing | 0.992 | D | 0.616 | neutral | None | None | None | None | I |
| V/Y | 0.7677 | likely_pathogenic | 0.7396 | pathogenic | -1.129 | Destabilizing | 0.92 | D | 0.469 | neutral | None | None | None | None | I |
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.