Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33363 | 100312;100313;100314 | chr2:178537022;178537021;178537020 | chr2:179401749;179401748;179401747 |
| N2AB | 31722 | 95389;95390;95391 | chr2:178537022;178537021;178537020 | chr2:179401749;179401748;179401747 |
| N2A | 30795 | 92608;92609;92610 | chr2:178537022;178537021;178537020 | chr2:179401749;179401748;179401747 |
| N2B | 24298 | 73117;73118;73119 | chr2:178537022;178537021;178537020 | chr2:179401749;179401748;179401747 |
| Novex-1 | 24423 | 73492;73493;73494 | chr2:178537022;178537021;178537020 | chr2:179401749;179401748;179401747 |
| Novex-2 | 24490 | 73693;73694;73695 | chr2:178537022;178537021;178537020 | chr2:179401749;179401748;179401747 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | rs774468606  |
-0.516 | 0.999 | N | 0.605 | 0.376 | 0.480497669815 | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.02E-05 | 0 |
| Y/F | rs774468606 |
-0.516 | 0.999 | N | 0.605 | 0.376 | 0.480497669815 | 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 |
| Y/F | rs774468606 |
-0.516 | 0.999 | N | 0.605 | 0.376 | 0.480497669815 | gnomAD-4.0.0 | 8.6781E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18682E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7485 | likely_pathogenic | 0.7171 | pathogenic | -2.247 | Highly Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| Y/C | 0.2548 | likely_benign | 0.197 | benign | -0.884 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.465724539 | None | None | N |
| Y/D | 0.8031 | likely_pathogenic | 0.7272 | pathogenic | -1.471 | Destabilizing | 1.0 | D | 0.833 | deleterious | N | 0.456046263 | None | None | N |
| Y/E | 0.8881 | likely_pathogenic | 0.8656 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| Y/F | 0.1323 | likely_benign | 0.1355 | benign | -0.52 | Destabilizing | 0.999 | D | 0.605 | neutral | N | 0.432516043 | None | None | N |
| Y/G | 0.7786 | likely_pathogenic | 0.7274 | pathogenic | -2.633 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| Y/H | 0.2438 | likely_benign | 0.2177 | benign | -1.058 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.445098551 | None | None | N |
| Y/I | 0.6382 | likely_pathogenic | 0.6145 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| Y/K | 0.6693 | likely_pathogenic | 0.6495 | pathogenic | -1.128 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/L | 0.5745 | likely_pathogenic | 0.5553 | ambiguous | -1.016 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| Y/M | 0.796 | likely_pathogenic | 0.7775 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| Y/N | 0.4378 | ambiguous | 0.3897 | ambiguous | -1.679 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.45431268 | None | None | N |
| Y/P | 0.9938 | likely_pathogenic | 0.989 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| Y/Q | 0.6654 | likely_pathogenic | 0.6313 | pathogenic | -1.469 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| Y/R | 0.4402 | ambiguous | 0.4107 | ambiguous | -0.959 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| Y/S | 0.4154 | ambiguous | 0.3672 | ambiguous | -2.219 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.413466135 | None | None | N |
| Y/T | 0.6267 | likely_pathogenic | 0.5995 | pathogenic | -1.928 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| Y/V | 0.5544 | ambiguous | 0.5273 | ambiguous | -1.431 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/W | 0.5493 | ambiguous | 0.5075 | ambiguous | 0.156 | Stabilizing | 1.0 | D | 0.757 | 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.