Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1350 | 4273;4274;4275 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
| N2AB | 1350 | 4273;4274;4275 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
| N2A | 1350 | 4273;4274;4275 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
| N2B | 1304 | 4135;4136;4137 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
| Novex-1 | 1304 | 4135;4136;4137 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
| Novex-2 | 1304 | 4135;4136;4137 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
| Novex-3 | 1350 | 4273;4274;4275 | chr2:178779034;178779033;178779032 | chr2:179643761;179643760;179643759 |
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 | rs550101167  |
-0.87 | 1.0 | D | 0.758 | 0.696 | None | gnomAD-2.1.1 | 2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.54E-05 | 0 |
| R/C | rs550101167 |
-0.87 | 1.0 | D | 0.758 | 0.696 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07469E-04 | 0 |
| R/C | rs550101167 |
-0.87 | 1.0 | D | 0.758 | 0.696 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/C | rs550101167 |
-0.87 | 1.0 | D | 0.758 | 0.696 | None | gnomAD-4.0.0 | 9.29395E-06 | None | None | None | None | N | None | 1.33323E-05 | 1.66644E-05 | None | 0 | 0 | None | 0 | 0 | 8.47502E-06 | 1.09808E-05 | 3.19959E-05 |
| R/H | rs539470256 |
-1.385 | 1.0 | N | 0.759 | 0.549 | None | gnomAD-2.1.1 | 1.20597E-04 | None | None | None | None | N | None | 0 | 2.2604E-04 | None | 0 | 1.50905E-04 | None | 5.8812E-04 | None | 7.97E-05 | 2.34E-05 | 0 |
| R/H | rs539470256 |
-1.385 | 1.0 | N | 0.759 | 0.549 | None | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 1.92382E-04 | None | 0 | 0 | 1.02899E-04 | 6.21375E-04 | 0 |
| R/H | rs539470256 |
-1.385 | 1.0 | N | 0.759 | 0.549 | None | 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 | rs539470256 |
-1.385 | 1.0 | N | 0.759 | 0.549 | None | gnomAD-4.0.0 | 6.56751E-05 | None | None | None | None | N | None | 0 | 1.33324E-04 | None | 0 | 8.91902E-05 | None | 4.68691E-05 | 1.64962E-04 | 3.30521E-05 | 4.94093E-04 | 9.59908E-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 | 0.7549 | likely_pathogenic | 0.797 | pathogenic | -1.039 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| R/C | 0.3178 | likely_benign | 0.3569 | ambiguous | -1.06 | Destabilizing | 1.0 | D | 0.758 | deleterious | D | 0.585497697 | None | None | N |
| R/D | 0.9208 | likely_pathogenic | 0.9364 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/E | 0.7024 | likely_pathogenic | 0.7375 | pathogenic | -0.063 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| R/F | 0.7999 | likely_pathogenic | 0.8266 | pathogenic | -0.988 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/G | 0.7239 | likely_pathogenic | 0.7721 | pathogenic | -1.317 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.584508556 | None | None | N |
| R/H | 0.1292 | likely_benign | 0.1485 | benign | -1.456 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.461663826 | None | None | N |
| R/I | 0.522 | ambiguous | 0.5537 | ambiguous | -0.298 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/K | 0.218 | likely_benign | 0.2437 | benign | -1.086 | Destabilizing | 0.998 | D | 0.525 | neutral | None | None | None | None | N |
| R/L | 0.5004 | ambiguous | 0.5463 | ambiguous | -0.298 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.476012004 | None | None | N |
| R/M | 0.5911 | likely_pathogenic | 0.6464 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/N | 0.8121 | likely_pathogenic | 0.8446 | pathogenic | -0.469 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/P | 0.9916 | likely_pathogenic | 0.9929 | pathogenic | -0.526 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | D | 0.585356162 | None | None | N |
| R/Q | 0.1716 | likely_benign | 0.1974 | benign | -0.729 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/S | 0.7556 | likely_pathogenic | 0.8006 | pathogenic | -1.322 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.443965984 | None | None | N |
| R/T | 0.528 | ambiguous | 0.5829 | pathogenic | -1.051 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/V | 0.5885 | likely_pathogenic | 0.6241 | pathogenic | -0.526 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/W | 0.4025 | ambiguous | 0.4463 | ambiguous | -0.598 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| R/Y | 0.6112 | likely_pathogenic | 0.6547 | pathogenic | -0.318 | Destabilizing | 1.0 | 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.