Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4943 | 15052;15053;15054 | chr2:178735619;178735618;178735617 | chr2:179600346;179600345;179600344 |
| N2AB | 4626 | 14101;14102;14103 | chr2:178735619;178735618;178735617 | chr2:179600346;179600345;179600344 |
| N2A | 3699 | 11320;11321;11322 | chr2:178735619;178735618;178735617 | chr2:179600346;179600345;179600344 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs540497678  |
-2.63 | 1.0 | D | 0.807 | 0.325 | 0.420939154896 | gnomAD-2.1.1 | 7.65E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.21362E-04 | None | 0 | 0 | 0 |
| A/E | rs540497678 |
-2.63 | 1.0 | D | 0.807 | 0.325 | 0.420939154896 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.29531E-04 | 0 |
| A/E | rs540497678 |
-2.63 | 1.0 | D | 0.807 | 0.325 | 0.420939154896 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/E | rs540497678 |
-2.63 | 1.0 | D | 0.807 | 0.325 | 0.420939154896 | gnomAD-4.0.0 | 3.5944E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47643E-07 | 6.25961E-04 | 0 |
| A/G | rs540497678 |
-1.719 | 0.999 | N | 0.642 | 0.318 | 0.281381271821 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/T | rs2081309584 |
None | 0.996 | N | 0.66 | 0.298 | 0.289474373501 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs2081309584 |
None | 0.996 | N | 0.66 | 0.298 | 0.289474373501 | gnomAD-4.0.0 | 3.84427E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17958E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.599 | likely_pathogenic | 0.6054 | pathogenic | -0.509 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| A/D | 0.9426 | likely_pathogenic | 0.9497 | pathogenic | -2.001 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| A/E | 0.899 | likely_pathogenic | 0.9103 | pathogenic | -1.783 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.533940992 | None | None | N |
| A/F | 0.6701 | likely_pathogenic | 0.654 | pathogenic | -0.414 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| A/G | 0.2437 | likely_benign | 0.2433 | benign | -1.204 | Destabilizing | 0.999 | D | 0.642 | neutral | N | 0.352048558 | None | None | N |
| A/H | 0.9262 | likely_pathogenic | 0.9312 | pathogenic | -1.855 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| A/I | 0.416 | ambiguous | 0.4262 | ambiguous | 0.613 | Stabilizing | 0.994 | D | 0.745 | deleterious | None | None | None | None | N |
| A/K | 0.9598 | likely_pathogenic | 0.9637 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| A/L | 0.3782 | ambiguous | 0.3699 | ambiguous | 0.613 | Stabilizing | 0.994 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/M | 0.4929 | ambiguous | 0.488 | ambiguous | 0.418 | Stabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| A/N | 0.8612 | likely_pathogenic | 0.8757 | pathogenic | -1.003 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| A/P | 0.6757 | likely_pathogenic | 0.7217 | pathogenic | 0.214 | Stabilizing | 1.0 | D | 0.839 | deleterious | D | 0.601598279 | None | None | N |
| A/Q | 0.8774 | likely_pathogenic | 0.886 | pathogenic | -0.759 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/R | 0.9185 | likely_pathogenic | 0.9232 | pathogenic | -0.962 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| A/S | 0.2001 | likely_benign | 0.2055 | benign | -1.374 | Destabilizing | 0.998 | D | 0.658 | neutral | N | 0.430931356 | None | None | N |
| A/T | 0.2049 | likely_benign | 0.2103 | benign | -1.031 | Destabilizing | 0.996 | D | 0.66 | neutral | N | 0.492479165 | None | None | N |
| A/V | 0.1981 | likely_benign | 0.1985 | benign | 0.214 | Stabilizing | 0.884 | D | 0.432 | neutral | N | 0.509424579 | None | None | N |
| A/W | 0.9606 | likely_pathogenic | 0.961 | pathogenic | -1.31 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| A/Y | 0.8624 | likely_pathogenic | 0.8582 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.847 | 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.