Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20047 | 60364;60365;60366 | chr2:178591680;178591679;178591678 | chr2:179456407;179456406;179456405 |
| N2AB | 18406 | 55441;55442;55443 | chr2:178591680;178591679;178591678 | chr2:179456407;179456406;179456405 |
| N2A | 17479 | 52660;52661;52662 | chr2:178591680;178591679;178591678 | chr2:179456407;179456406;179456405 |
| N2B | 10982 | 33169;33170;33171 | chr2:178591680;178591679;178591678 | chr2:179456407;179456406;179456405 |
| Novex-1 | 11107 | 33544;33545;33546 | chr2:178591680;178591679;178591678 | chr2:179456407;179456406;179456405 |
| Novex-2 | 11174 | 33745;33746;33747 | chr2:178591680;178591679;178591678 | chr2:179456407;179456406;179456405 |
| 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/K | rs371060708  |
-1.146 | None | N | 0.269 | 0.05 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.44E-05 | 0 |
| R/K | rs371060708 |
-1.146 | None | N | 0.269 | 0.05 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 4.78469E-04 |
| R/K | rs371060708 |
-1.146 | None | N | 0.269 | 0.05 | None | gnomAD-4.0.0 | 8.2439E-05 | None | None | None | None | N | None | 1.33554E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.11058E-04 | 0 | 1.60128E-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 | 0.6238 | likely_pathogenic | 0.5021 | ambiguous | -1.696 | Destabilizing | 0.116 | N | 0.515 | neutral | None | None | None | None | N |
| R/C | 0.1895 | likely_benign | 0.1673 | benign | -1.728 | Destabilizing | 0.981 | D | 0.637 | neutral | None | None | None | None | N |
| R/D | 0.8808 | likely_pathogenic | 0.8188 | pathogenic | -0.766 | Destabilizing | 0.388 | N | 0.599 | neutral | None | None | None | None | N |
| R/E | 0.5718 | likely_pathogenic | 0.4806 | ambiguous | -0.562 | Destabilizing | 0.116 | N | 0.531 | neutral | None | None | None | None | N |
| R/F | 0.6308 | likely_pathogenic | 0.5438 | ambiguous | -0.992 | Destabilizing | 0.69 | D | 0.629 | neutral | None | None | None | None | N |
| R/G | 0.5978 | likely_pathogenic | 0.467 | ambiguous | -2.043 | Highly Destabilizing | 0.324 | N | 0.564 | neutral | N | 0.470394506 | None | None | N |
| R/H | 0.1251 | likely_benign | 0.1021 | benign | -1.977 | Destabilizing | 0.818 | D | 0.581 | neutral | None | None | None | None | N |
| R/I | 0.2711 | likely_benign | 0.2134 | benign | -0.702 | Destabilizing | 0.001 | N | 0.545 | neutral | N | 0.491929706 | None | None | N |
| R/K | 0.1141 | likely_benign | 0.0878 | benign | -1.329 | Destabilizing | None | N | 0.269 | neutral | N | 0.446271987 | None | None | N |
| R/L | 0.2673 | likely_benign | 0.2075 | benign | -0.702 | Destabilizing | 0.043 | N | 0.547 | neutral | None | None | None | None | N |
| R/M | 0.3239 | likely_benign | 0.2495 | benign | -1.229 | Destabilizing | 0.69 | D | 0.601 | neutral | None | None | None | None | N |
| R/N | 0.6951 | likely_pathogenic | 0.5829 | pathogenic | -1.189 | Destabilizing | 0.388 | N | 0.503 | neutral | None | None | None | None | N |
| R/P | 0.9819 | likely_pathogenic | 0.9754 | pathogenic | -1.019 | Destabilizing | 0.818 | D | 0.622 | neutral | None | None | None | None | N |
| R/Q | 0.1343 | likely_benign | 0.1098 | benign | -1.076 | Destabilizing | 0.388 | N | 0.532 | neutral | None | None | None | None | N |
| R/S | 0.6364 | likely_pathogenic | 0.5041 | ambiguous | -2.042 | Highly Destabilizing | 0.324 | N | 0.539 | neutral | N | 0.466492543 | None | None | N |
| R/T | 0.306 | likely_benign | 0.2169 | benign | -1.63 | Destabilizing | 0.324 | N | 0.529 | neutral | N | 0.470570212 | None | None | N |
| R/V | 0.3712 | ambiguous | 0.2986 | benign | -1.019 | Destabilizing | 0.098 | N | 0.569 | neutral | None | None | None | None | N |
| R/W | 0.2748 | likely_benign | 0.2372 | benign | -0.547 | Destabilizing | 0.981 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/Y | 0.4802 | ambiguous | 0.4167 | ambiguous | -0.353 | Destabilizing | 0.818 | D | 0.629 | neutral | 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.