Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28771 | 86536;86537;86538 | chr2:178559821;178559820;178559819 | chr2:179424548;179424547;179424546 |
| N2AB | 27130 | 81613;81614;81615 | chr2:178559821;178559820;178559819 | chr2:179424548;179424547;179424546 |
| N2A | 26203 | 78832;78833;78834 | chr2:178559821;178559820;178559819 | chr2:179424548;179424547;179424546 |
| N2B | 19706 | 59341;59342;59343 | chr2:178559821;178559820;178559819 | chr2:179424548;179424547;179424546 |
| Novex-1 | 19831 | 59716;59717;59718 | chr2:178559821;178559820;178559819 | chr2:179424548;179424547;179424546 |
| Novex-2 | 19898 | 59917;59918;59919 | chr2:178559821;178559820;178559819 | chr2:179424548;179424547;179424546 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs760184584  |
-0.043 | 0.698 | N | 0.456 | 0.438 | 0.514811571519 | gnomAD-2.1.1 | 8.12E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11371E-04 | None | 0 | None | 0 | 0 | 0 |
| S/L | rs760184584 |
-0.043 | 0.698 | N | 0.456 | 0.438 | 0.514811571519 | gnomAD-4.0.0 | 3.19947E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.54723E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs369269686 |
-0.024 | 0.97 | N | 0.487 | 0.335 | None | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | I | None | 1.65344E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs369269686 |
-0.024 | 0.97 | N | 0.487 | 0.335 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs369269686 |
-0.024 | 0.97 | N | 0.487 | 0.335 | None | gnomAD-4.0.0 | 5.58885E-06 | None | None | None | None | I | None | 1.20163E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0932 | likely_benign | 0.0901 | benign | -0.823 | Destabilizing | 0.014 | N | 0.231 | neutral | N | 0.503098344 | None | None | I |
| S/C | 0.1667 | likely_benign | 0.1698 | benign | -0.476 | Destabilizing | 0.994 | D | 0.54 | neutral | None | None | None | None | I |
| S/D | 0.6435 | likely_pathogenic | 0.6598 | pathogenic | 0.172 | Stabilizing | 0.926 | D | 0.385 | neutral | None | None | None | None | I |
| S/E | 0.8135 | likely_pathogenic | 0.8102 | pathogenic | 0.124 | Stabilizing | 0.86 | D | 0.409 | neutral | None | None | None | None | I |
| S/F | 0.4396 | ambiguous | 0.424 | ambiguous | -1.256 | Destabilizing | 0.978 | D | 0.591 | neutral | None | None | None | None | I |
| S/G | 0.1234 | likely_benign | 0.122 | benign | -1.0 | Destabilizing | 0.754 | D | 0.423 | neutral | None | None | None | None | I |
| S/H | 0.5992 | likely_pathogenic | 0.6083 | pathogenic | -1.467 | Destabilizing | 0.043 | N | 0.355 | neutral | None | None | None | None | I |
| S/I | 0.3775 | ambiguous | 0.3601 | ambiguous | -0.469 | Destabilizing | 0.956 | D | 0.577 | neutral | None | None | None | None | I |
| S/K | 0.8739 | likely_pathogenic | 0.8849 | pathogenic | -0.534 | Destabilizing | 0.86 | D | 0.401 | neutral | None | None | None | None | I |
| S/L | 0.1943 | likely_benign | 0.1787 | benign | -0.469 | Destabilizing | 0.698 | D | 0.456 | neutral | N | 0.476660433 | None | None | I |
| S/M | 0.3727 | ambiguous | 0.3592 | ambiguous | -0.125 | Destabilizing | 0.998 | D | 0.519 | neutral | None | None | None | None | I |
| S/N | 0.249 | likely_benign | 0.2483 | benign | -0.357 | Destabilizing | 0.86 | D | 0.427 | neutral | None | None | None | None | I |
| S/P | 0.1829 | likely_benign | 0.1884 | benign | -0.557 | Destabilizing | 0.97 | D | 0.487 | neutral | N | 0.432832969 | None | None | I |
| S/Q | 0.7323 | likely_pathogenic | 0.7336 | pathogenic | -0.575 | Destabilizing | 0.978 | D | 0.443 | neutral | None | None | None | None | I |
| S/R | 0.8183 | likely_pathogenic | 0.8275 | pathogenic | -0.376 | Destabilizing | 0.978 | D | 0.493 | neutral | None | None | None | None | I |
| S/T | 0.0971 | likely_benign | 0.0968 | benign | -0.487 | Destabilizing | 0.822 | D | 0.427 | neutral | N | 0.445722121 | None | None | I |
| S/V | 0.2955 | likely_benign | 0.2801 | benign | -0.557 | Destabilizing | 0.915 | D | 0.481 | neutral | None | None | None | None | I |
| S/W | 0.6833 | likely_pathogenic | 0.6874 | pathogenic | -1.169 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | I |
| S/Y | 0.412 | ambiguous | 0.4033 | ambiguous | -0.921 | Destabilizing | 0.956 | D | 0.583 | 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.