Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33557 | 100894;100895;100896 | chr2:178536078;178536077;178536076 | chr2:179400805;179400804;179400803 |
| N2AB | 31916 | 95971;95972;95973 | chr2:178536078;178536077;178536076 | chr2:179400805;179400804;179400803 |
| N2A | 30989 | 93190;93191;93192 | chr2:178536078;178536077;178536076 | chr2:179400805;179400804;179400803 |
| N2B | 24492 | 73699;73700;73701 | chr2:178536078;178536077;178536076 | chr2:179400805;179400804;179400803 |
| Novex-1 | 24617 | 74074;74075;74076 | chr2:178536078;178536077;178536076 | chr2:179400805;179400804;179400803 |
| Novex-2 | 24684 | 74275;74276;74277 | chr2:178536078;178536077;178536076 | chr2:179400805;179400804;179400803 |
| 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/M | rs771784438  |
-1.837 | 0.233 | D | 0.413 | 0.468 | 0.594650670498 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1007331943 |
-3.35 | 0.997 | D | 0.722 | 0.794 | 0.862868373484 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| I/T | rs1007331943 |
-3.35 | 0.997 | D | 0.722 | 0.794 | 0.862868373484 | gnomAD-4.0.0 | 1.99117E-05 | None | None | None | None | N | None | 2.99796E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.52657E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9699 | likely_pathogenic | 0.9683 | pathogenic | -2.925 | Highly Destabilizing | 0.96 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.9822 | likely_pathogenic | 0.9822 | pathogenic | -2.234 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9993 | pathogenic | -3.572 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| I/E | 0.9989 | likely_pathogenic | 0.9978 | pathogenic | -3.245 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| I/F | 0.6738 | likely_pathogenic | 0.6684 | pathogenic | -1.677 | Destabilizing | 0.98 | D | 0.686 | prob.neutral | D | 0.543468432 | None | None | N |
| I/G | 0.9984 | likely_pathogenic | 0.9976 | pathogenic | -3.553 | Highly Destabilizing | 0.997 | D | 0.853 | deleterious | None | None | None | None | N |
| I/H | 0.9972 | likely_pathogenic | 0.9958 | pathogenic | -3.185 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| I/K | 0.9966 | likely_pathogenic | 0.9935 | pathogenic | -2.191 | Highly Destabilizing | 0.993 | D | 0.858 | deleterious | None | None | None | None | N |
| I/L | 0.4094 | ambiguous | 0.3892 | ambiguous | -1.036 | Destabilizing | 0.032 | N | 0.4 | neutral | D | 0.534237336 | None | None | N |
| I/M | 0.4832 | ambiguous | 0.4345 | ambiguous | -1.289 | Destabilizing | 0.233 | N | 0.413 | neutral | D | 0.585550955 | None | None | N |
| I/N | 0.9954 | likely_pathogenic | 0.9924 | pathogenic | -2.889 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.60321511 | None | None | N |
| I/P | 0.9988 | likely_pathogenic | 0.9978 | pathogenic | -1.657 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| I/Q | 0.997 | likely_pathogenic | 0.9944 | pathogenic | -2.539 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| I/R | 0.9942 | likely_pathogenic | 0.9897 | pathogenic | -2.203 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| I/S | 0.9892 | likely_pathogenic | 0.9859 | pathogenic | -3.495 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.619234471 | None | None | N |
| I/T | 0.9624 | likely_pathogenic | 0.9593 | pathogenic | -3.0 | Highly Destabilizing | 0.997 | D | 0.722 | prob.delet. | D | 0.593292751 | None | None | N |
| I/V | 0.1583 | likely_benign | 0.2105 | benign | -1.657 | Destabilizing | 0.008 | N | 0.29 | neutral | D | 0.529437021 | None | None | N |
| I/W | 0.9954 | likely_pathogenic | 0.9929 | pathogenic | -2.095 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| I/Y | 0.9869 | likely_pathogenic | 0.9823 | pathogenic | -1.902 | Destabilizing | 0.998 | D | 0.755 | 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.