Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3427 | 10504;10505;10506 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
| N2AB | 3427 | 10504;10505;10506 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
| N2A | 3427 | 10504;10505;10506 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
| N2B | 3381 | 10366;10367;10368 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
| Novex-1 | 3381 | 10366;10367;10368 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
| Novex-2 | 3381 | 10366;10367;10368 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
| Novex-3 | 3427 | 10504;10505;10506 | chr2:178759008;178759007;178759006 | chr2:179623735;179623734;179623733 |
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/N | rs368333336  |
-0.461 | 0.961 | D | 0.715 | 0.376 | None | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | N | None | 1.20154E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs368333336 |
-0.461 | 0.961 | D | 0.715 | 0.376 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.4476E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs368333336 |
-0.461 | 0.961 | D | 0.715 | 0.376 | None | gnomAD-4.0.0 | 8.05505E-06 | None | None | None | None | N | None | 1.73514E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs368333336 |
None | 0.801 | N | 0.65 | 0.259 | 0.242825505644 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs368333336 |
None | 0.801 | N | 0.65 | 0.259 | 0.242825505644 | gnomAD-4.0.0 | 6.57151E-06 | None | None | None | None | N | None | 0 | 6.54365E-05 | 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 | 0.1241 | likely_benign | 0.1238 | benign | -0.842 | Destabilizing | 0.325 | N | 0.512 | neutral | None | None | None | None | N |
| S/C | 0.142 | likely_benign | 0.1209 | benign | -0.393 | Destabilizing | 0.005 | N | 0.377 | neutral | N | 0.444941416 | None | None | N |
| S/D | 0.8526 | likely_pathogenic | 0.9141 | pathogenic | -0.109 | Destabilizing | 0.971 | D | 0.717 | prob.delet. | None | None | None | None | N |
| S/E | 0.9126 | likely_pathogenic | 0.9532 | pathogenic | -0.01 | Destabilizing | 0.971 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/F | 0.6992 | likely_pathogenic | 0.7437 | pathogenic | -0.848 | Destabilizing | 0.991 | D | 0.756 | deleterious | None | None | None | None | N |
| S/G | 0.1831 | likely_benign | 0.1924 | benign | -1.179 | Destabilizing | 0.891 | D | 0.661 | neutral | D | 0.547948705 | None | None | N |
| S/H | 0.7878 | likely_pathogenic | 0.8638 | pathogenic | -1.475 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | N |
| S/I | 0.6137 | likely_pathogenic | 0.6245 | pathogenic | -0.02 | Destabilizing | 0.934 | D | 0.766 | deleterious | N | 0.50787821 | None | None | N |
| S/K | 0.9738 | likely_pathogenic | 0.9876 | pathogenic | -0.126 | Destabilizing | 0.971 | D | 0.72 | prob.delet. | None | None | None | None | N |
| S/L | 0.3851 | ambiguous | 0.3824 | ambiguous | -0.02 | Destabilizing | 0.728 | D | 0.675 | prob.neutral | None | None | None | None | N |
| S/M | 0.5835 | likely_pathogenic | 0.5596 | ambiguous | 0.057 | Stabilizing | 0.991 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/N | 0.5043 | ambiguous | 0.5876 | pathogenic | -0.394 | Destabilizing | 0.961 | D | 0.715 | prob.delet. | D | 0.540730222 | None | None | N |
| S/P | 0.9815 | likely_pathogenic | 0.9805 | pathogenic | -0.259 | Destabilizing | 0.991 | D | 0.748 | deleterious | None | None | None | None | N |
| S/Q | 0.878 | likely_pathogenic | 0.9313 | pathogenic | -0.35 | Destabilizing | 0.991 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/R | 0.9403 | likely_pathogenic | 0.9688 | pathogenic | -0.302 | Destabilizing | 0.989 | D | 0.75 | deleterious | N | 0.510044226 | None | None | N |
| S/T | 0.1426 | likely_benign | 0.1188 | benign | -0.36 | Destabilizing | 0.801 | D | 0.65 | neutral | N | 0.498740977 | None | None | N |
| S/V | 0.4666 | ambiguous | 0.4679 | ambiguous | -0.259 | Destabilizing | 0.842 | D | 0.702 | prob.neutral | None | None | None | None | N |
| S/W | 0.8681 | likely_pathogenic | 0.8904 | pathogenic | -0.859 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| S/Y | 0.6391 | likely_pathogenic | 0.7162 | pathogenic | -0.511 | Destabilizing | 0.991 | D | 0.741 | 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.