Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19216 | 57871;57872;57873 | chr2:178595708;178595707;178595706 | chr2:179460435;179460434;179460433 |
| N2AB | 17575 | 52948;52949;52950 | chr2:178595708;178595707;178595706 | chr2:179460435;179460434;179460433 |
| N2A | 16648 | 50167;50168;50169 | chr2:178595708;178595707;178595706 | chr2:179460435;179460434;179460433 |
| N2B | 10151 | 30676;30677;30678 | chr2:178595708;178595707;178595706 | chr2:179460435;179460434;179460433 |
| Novex-1 | 10276 | 31051;31052;31053 | chr2:178595708;178595707;178595706 | chr2:179460435;179460434;179460433 |
| Novex-2 | 10343 | 31252;31253;31254 | chr2:178595708;178595707;178595706 | chr2:179460435;179460434;179460433 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs374058726  |
-1.529 | 0.006 | N | 0.24 | 0.056 | None | gnomAD-2.1.1 | 3.64789E-04 | None | None | None | None | I | None | 8.52E-05 | 1.62112E-03 | None | 0 | 0 | None | 0 | None | 0 | 2.74079E-04 | 1.0043E-03 |
| I/V | rs374058726 |
-1.529 | 0.006 | N | 0.24 | 0.056 | None | gnomAD-3.1.2 | 2.56501E-04 | None | None | None | None | I | None | 9.66E-05 | 6.5505E-04 | 0 | 0 | 0 | None | 0 | 0 | 3.38285E-04 | 0 | 9.56938E-04 |
| I/V | rs374058726 |
-1.529 | 0.006 | N | 0.24 | 0.056 | None | gnomAD-4.0.0 | 3.20132E-04 | None | None | None | None | I | None | 6.68199E-05 | 1.41257E-03 | None | 0 | 0 | None | 1.56794E-05 | 0 | 3.47289E-04 | 2.22936E-05 | 2.24661E-04 |
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 | 0.9651 | likely_pathogenic | 0.9762 | pathogenic | -2.328 | Highly Destabilizing | 0.754 | D | 0.691 | prob.neutral | None | None | None | None | I |
| I/C | 0.9664 | likely_pathogenic | 0.9775 | pathogenic | -1.579 | Destabilizing | 0.994 | D | 0.747 | deleterious | None | None | None | None | I |
| I/D | 0.9989 | likely_pathogenic | 0.9992 | pathogenic | -2.413 | Highly Destabilizing | 0.993 | D | 0.839 | deleterious | None | None | None | None | I |
| I/E | 0.9956 | likely_pathogenic | 0.9969 | pathogenic | -2.342 | Highly Destabilizing | 0.978 | D | 0.84 | deleterious | None | None | None | None | I |
| I/F | 0.9441 | likely_pathogenic | 0.9582 | pathogenic | -1.69 | Destabilizing | 0.942 | D | 0.757 | deleterious | N | 0.515320111 | None | None | I |
| I/G | 0.9964 | likely_pathogenic | 0.9974 | pathogenic | -2.735 | Highly Destabilizing | 0.978 | D | 0.835 | deleterious | None | None | None | None | I |
| I/H | 0.9968 | likely_pathogenic | 0.9977 | pathogenic | -2.043 | Highly Destabilizing | 0.998 | D | 0.808 | deleterious | None | None | None | None | I |
| I/K | 0.9916 | likely_pathogenic | 0.9938 | pathogenic | -1.702 | Destabilizing | 0.978 | D | 0.839 | deleterious | None | None | None | None | I |
| I/L | 0.402 | ambiguous | 0.4403 | ambiguous | -1.219 | Destabilizing | 0.294 | N | 0.471 | neutral | D | 0.526893215 | None | None | I |
| I/M | 0.5845 | likely_pathogenic | 0.634 | pathogenic | -0.919 | Destabilizing | 0.942 | D | 0.728 | prob.delet. | D | 0.524602956 | None | None | I |
| I/N | 0.9815 | likely_pathogenic | 0.9862 | pathogenic | -1.692 | Destabilizing | 0.99 | D | 0.843 | deleterious | D | 0.536973219 | None | None | I |
| I/P | 0.9636 | likely_pathogenic | 0.98 | pathogenic | -1.563 | Destabilizing | 0.993 | D | 0.847 | deleterious | None | None | None | None | I |
| I/Q | 0.9928 | likely_pathogenic | 0.9948 | pathogenic | -1.821 | Destabilizing | 0.993 | D | 0.839 | deleterious | None | None | None | None | I |
| I/R | 0.9884 | likely_pathogenic | 0.9922 | pathogenic | -1.114 | Destabilizing | 0.978 | D | 0.842 | deleterious | None | None | None | None | I |
| I/S | 0.9811 | likely_pathogenic | 0.9862 | pathogenic | -2.325 | Highly Destabilizing | 0.942 | D | 0.806 | deleterious | D | 0.524856445 | None | None | I |
| I/T | 0.9466 | likely_pathogenic | 0.9601 | pathogenic | -2.133 | Highly Destabilizing | 0.822 | D | 0.784 | deleterious | N | 0.501979251 | None | None | I |
| I/V | 0.077 | likely_benign | 0.0852 | benign | -1.563 | Destabilizing | 0.006 | N | 0.24 | neutral | N | 0.499629256 | None | None | I |
| I/W | 0.9985 | likely_pathogenic | 0.999 | pathogenic | -1.909 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | I |
| I/Y | 0.993 | likely_pathogenic | 0.9951 | pathogenic | -1.677 | Destabilizing | 0.978 | D | 0.779 | deleterious | 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.