Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19232 | 57919;57920;57921 | chr2:178595660;178595659;178595658 | chr2:179460387;179460386;179460385 |
| N2AB | 17591 | 52996;52997;52998 | chr2:178595660;178595659;178595658 | chr2:179460387;179460386;179460385 |
| N2A | 16664 | 50215;50216;50217 | chr2:178595660;178595659;178595658 | chr2:179460387;179460386;179460385 |
| N2B | 10167 | 30724;30725;30726 | chr2:178595660;178595659;178595658 | chr2:179460387;179460386;179460385 |
| Novex-1 | 10292 | 31099;31100;31101 | chr2:178595660;178595659;178595658 | chr2:179460387;179460386;179460385 |
| Novex-2 | 10359 | 31300;31301;31302 | chr2:178595660;178595659;178595658 | chr2:179460387;179460386;179460385 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs376457991  |
0.102 | 1.0 | N | 0.743 | 0.398 | 0.550885202691 | gnomAD-2.1.1 | 8.34E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.88E-05 | None | 0 | 0 | 0 |
| T/I | rs376457991 |
0.102 | 1.0 | N | 0.743 | 0.398 | 0.550885202691 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| T/I | rs376457991 |
0.102 | 1.0 | N | 0.743 | 0.398 | 0.550885202691 | gnomAD-4.0.0 | 4.35269E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.45434E-05 | 4.81433E-05 |
| T/N | rs376457991 |
-0.549 | 1.0 | N | 0.749 | 0.358 | None | gnomAD-2.1.1 | 4.17E-06 | None | None | None | None | I | None | 6.79E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/N | rs376457991 |
-0.549 | 1.0 | N | 0.749 | 0.358 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs376457991 |
-0.549 | 1.0 | N | 0.749 | 0.358 | None | gnomAD-4.0.0 | 1.24372E-06 | None | None | None | None | I | None | 1.33672E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.49404E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1423 | likely_benign | 0.1385 | benign | -0.661 | Destabilizing | 0.999 | D | 0.559 | neutral | N | 0.500047757 | None | None | I |
| T/C | 0.5639 | ambiguous | 0.5352 | ambiguous | -0.47 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| T/D | 0.7016 | likely_pathogenic | 0.7396 | pathogenic | 0.083 | Stabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| T/E | 0.5003 | ambiguous | 0.5625 | ambiguous | 0.083 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| T/F | 0.3438 | ambiguous | 0.3736 | ambiguous | -0.742 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| T/G | 0.4258 | ambiguous | 0.4077 | ambiguous | -0.907 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| T/H | 0.3905 | ambiguous | 0.4155 | ambiguous | -1.085 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| T/I | 0.1986 | likely_benign | 0.2109 | benign | -0.106 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.490062836 | None | None | I |
| T/K | 0.3924 | ambiguous | 0.4621 | ambiguous | -0.624 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| T/L | 0.129 | likely_benign | 0.1339 | benign | -0.106 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | I |
| T/M | 0.094 | likely_benign | 0.0953 | benign | -0.046 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| T/N | 0.1784 | likely_benign | 0.1804 | benign | -0.574 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.521441749 | None | None | I |
| T/P | 0.7409 | likely_pathogenic | 0.7669 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.486523752 | None | None | I |
| T/Q | 0.3064 | likely_benign | 0.3288 | benign | -0.683 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| T/R | 0.401 | ambiguous | 0.4774 | ambiguous | -0.389 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| T/S | 0.1518 | likely_benign | 0.1532 | benign | -0.852 | Destabilizing | 0.999 | D | 0.559 | neutral | N | 0.490062836 | None | None | I |
| T/V | 0.17 | likely_benign | 0.1698 | benign | -0.258 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | I |
| T/W | 0.784 | likely_pathogenic | 0.7924 | pathogenic | -0.716 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| T/Y | 0.3928 | ambiguous | 0.4236 | ambiguous | -0.47 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | 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.