Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19287 | 58084;58085;58086 | chr2:178594635;178594634;178594633 | chr2:179459362;179459361;179459360 |
| N2AB | 17646 | 53161;53162;53163 | chr2:178594635;178594634;178594633 | chr2:179459362;179459361;179459360 |
| N2A | 16719 | 50380;50381;50382 | chr2:178594635;178594634;178594633 | chr2:179459362;179459361;179459360 |
| N2B | 10222 | 30889;30890;30891 | chr2:178594635;178594634;178594633 | chr2:179459362;179459361;179459360 |
| Novex-1 | 10347 | 31264;31265;31266 | chr2:178594635;178594634;178594633 | chr2:179459362;179459361;179459360 |
| Novex-2 | 10414 | 31465;31466;31467 | chr2:178594635;178594634;178594633 | chr2:179459362;179459361;179459360 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs372710684  |
-0.742 | 1.0 | N | 0.847 | 0.402 | None | gnomAD-2.1.1 | 3.31E-05 | None | None | None | None | N | None | 6.52E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.36E-05 | 0 |
| R/C | rs372710684 |
-0.742 | 1.0 | N | 0.847 | 0.402 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs372710684 |
-0.742 | 1.0 | N | 0.847 | 0.402 | None | gnomAD-4.0.0 | 1.18486E-05 | None | None | None | None | N | None | 4.03573E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.36229E-05 | 0 | 0 |
| R/G | rs372710684 |
None | 1.0 | N | 0.806 | 0.35 | 0.560115663565 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs372710684 |
None | 1.0 | N | 0.806 | 0.35 | 0.560115663565 | gnomAD-4.0.0 | 6.57748E-06 | None | None | None | None | N | None | 0 | 6.5505E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs371422299 |
-1.388 | 1.0 | N | 0.757 | 0.374 | 0.269111216191 | gnomAD-2.1.1 | 6.61E-05 | None | None | None | None | N | None | 0 | 2.39392E-04 | None | 1.04844E-04 | 1.13366E-04 | None | 0 | None | 0 | 2.73E-05 | 3.4188E-04 |
| R/H | rs371422299 |
-1.388 | 1.0 | N | 0.757 | 0.374 | 0.269111216191 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93874E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs371422299 |
-1.388 | 1.0 | N | 0.757 | 0.374 | 0.269111216191 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/H | rs371422299 |
-1.388 | 1.0 | N | 0.757 | 0.374 | 0.269111216191 | gnomAD-4.0.0 | 2.80602E-05 | None | None | None | None | N | None | 2.68565E-05 | 1.70137E-04 | None | 6.86153E-05 | 6.72284E-05 | None | 0 | 3.34113E-04 | 1.53255E-05 | 3.34971E-05 | 8.06088E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9204 | likely_pathogenic | 0.8604 | pathogenic | -0.892 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| R/C | 0.7267 | likely_pathogenic | 0.5978 | pathogenic | -0.785 | Destabilizing | 1.0 | D | 0.847 | deleterious | N | 0.513555772 | None | None | N |
| R/D | 0.9749 | likely_pathogenic | 0.9572 | pathogenic | 0.004 | Stabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/E | 0.9047 | likely_pathogenic | 0.8352 | pathogenic | 0.167 | Stabilizing | 0.999 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/F | 0.9588 | likely_pathogenic | 0.9211 | pathogenic | -0.459 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.9051 | likely_pathogenic | 0.8332 | pathogenic | -1.244 | Destabilizing | 1.0 | D | 0.806 | deleterious | N | 0.469634038 | None | None | N |
| R/H | 0.5889 | likely_pathogenic | 0.4706 | ambiguous | -1.514 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.513382413 | None | None | N |
| R/I | 0.8611 | likely_pathogenic | 0.7608 | pathogenic | 0.073 | Stabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| R/K | 0.4352 | ambiguous | 0.3636 | ambiguous | -0.769 | Destabilizing | 0.998 | D | 0.708 | prob.delet. | None | None | None | None | N |
| R/L | 0.8375 | likely_pathogenic | 0.7484 | pathogenic | 0.073 | Stabilizing | 1.0 | D | 0.806 | deleterious | N | 0.520751103 | None | None | N |
| R/M | 0.8659 | likely_pathogenic | 0.7738 | pathogenic | -0.376 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| R/N | 0.9585 | likely_pathogenic | 0.923 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| R/P | 0.8546 | likely_pathogenic | 0.7816 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.381353717 | None | None | N |
| R/Q | 0.5437 | ambiguous | 0.423 | ambiguous | -0.383 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/S | 0.9583 | likely_pathogenic | 0.9182 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.442596963 | None | None | N |
| R/T | 0.9275 | likely_pathogenic | 0.8598 | pathogenic | -0.747 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| R/V | 0.9 | likely_pathogenic | 0.8324 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| R/W | 0.7576 | likely_pathogenic | 0.6597 | pathogenic | -0.057 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| R/Y | 0.8877 | likely_pathogenic | 0.8189 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.836 | 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.