Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23368 | 70327;70328;70329 | chr2:178576030;178576029;178576028 | chr2:179440757;179440756;179440755 |
| N2AB | 21727 | 65404;65405;65406 | chr2:178576030;178576029;178576028 | chr2:179440757;179440756;179440755 |
| N2A | 20800 | 62623;62624;62625 | chr2:178576030;178576029;178576028 | chr2:179440757;179440756;179440755 |
| N2B | 14303 | 43132;43133;43134 | chr2:178576030;178576029;178576028 | chr2:179440757;179440756;179440755 |
| Novex-1 | 14428 | 43507;43508;43509 | chr2:178576030;178576029;178576028 | chr2:179440757;179440756;179440755 |
| Novex-2 | 14495 | 43708;43709;43710 | chr2:178576030;178576029;178576028 | chr2:179440757;179440756;179440755 |
| 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/N | None | None | 1.0 | N | 0.859 | 0.698 | 0.90350922459 | 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 |
| I/V | rs367914610  |
-1.415 | 0.993 | N | 0.353 | 0.25 | None | gnomAD-2.1.1 | 9.65E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 1.30779E-04 | None | 0 | 1.56345E-04 | 2.81057E-04 |
| I/V | rs367914610 |
-1.415 | 0.993 | N | 0.353 | 0.25 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 1.96515E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 9.5511E-04 |
| I/V | rs367914610 |
-1.415 | 0.993 | N | 0.353 | 0.25 | None | gnomAD-4.0.0 | 8.98834E-05 | None | None | None | None | N | None | 8.01089E-05 | 8.33611E-05 | None | 0 | 0 | None | 0 | 1.811E-03 | 7.88494E-05 | 1.2081E-04 | 3.04273E-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 | 0.8996 | likely_pathogenic | 0.9229 | pathogenic | -1.925 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| I/C | 0.9143 | likely_pathogenic | 0.9431 | pathogenic | -1.236 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/D | 0.9983 | likely_pathogenic | 0.9988 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/E | 0.9915 | likely_pathogenic | 0.9937 | pathogenic | -1.282 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/F | 0.3441 | ambiguous | 0.4506 | ambiguous | -1.238 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.47368874 | None | None | N |
| I/G | 0.9833 | likely_pathogenic | 0.9889 | pathogenic | -2.308 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| I/H | 0.9772 | likely_pathogenic | 0.986 | pathogenic | -1.475 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| I/K | 0.9731 | likely_pathogenic | 0.9809 | pathogenic | -1.416 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| I/L | 0.2359 | likely_benign | 0.2655 | benign | -0.919 | Destabilizing | 0.993 | D | 0.411 | neutral | N | 0.504606293 | None | None | N |
| I/M | 0.2443 | likely_benign | 0.2993 | benign | -0.732 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.492132153 | None | None | N |
| I/N | 0.9694 | likely_pathogenic | 0.9786 | pathogenic | -1.284 | Destabilizing | 1.0 | D | 0.859 | deleterious | N | 0.515351743 | None | None | N |
| I/P | 0.9927 | likely_pathogenic | 0.9947 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| I/Q | 0.9707 | likely_pathogenic | 0.9787 | pathogenic | -1.401 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| I/R | 0.9598 | likely_pathogenic | 0.971 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| I/S | 0.9424 | likely_pathogenic | 0.9561 | pathogenic | -1.967 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.492385643 | None | None | N |
| I/T | 0.9084 | likely_pathogenic | 0.9316 | pathogenic | -1.792 | Destabilizing | 1.0 | D | 0.768 | deleterious | D | 0.534139766 | None | None | N |
| I/V | 0.0977 | likely_benign | 0.1087 | benign | -1.224 | Destabilizing | 0.993 | D | 0.353 | neutral | N | 0.426787723 | None | None | N |
| I/W | 0.9681 | likely_pathogenic | 0.9814 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| I/Y | 0.8736 | likely_pathogenic | 0.9176 | pathogenic | -1.131 | Destabilizing | 1.0 | D | 0.816 | 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.