Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32213 | 96862;96863;96864 | chr2:178543336;178543335;178543334 | chr2:179408063;179408062;179408061 |
| N2AB | 30572 | 91939;91940;91941 | chr2:178543336;178543335;178543334 | chr2:179408063;179408062;179408061 |
| N2A | 29645 | 89158;89159;89160 | chr2:178543336;178543335;178543334 | chr2:179408063;179408062;179408061 |
| N2B | 23148 | 69667;69668;69669 | chr2:178543336;178543335;178543334 | chr2:179408063;179408062;179408061 |
| Novex-1 | 23273 | 70042;70043;70044 | chr2:178543336;178543335;178543334 | chr2:179408063;179408062;179408061 |
| Novex-2 | 23340 | 70243;70244;70245 | chr2:178543336;178543335;178543334 | chr2:179408063;179408062;179408061 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs764561909  |
0.117 | 0.996 | N | 0.653 | 0.29 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 1.30719E-04 | None | 0 | 2.34E-05 | 0 |
| D/N | rs764561909 |
0.117 | 0.996 | N | 0.653 | 0.29 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 9.66E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs764561909 |
0.117 | 0.996 | N | 0.653 | 0.29 | None | gnomAD-4.0.0 | 7.12644E-05 | None | None | None | None | N | None | 6.6761E-05 | 6.66844E-05 | None | 0 | 0 | None | 0 | 0 | 7.9674E-05 | 1.09789E-04 | 3.20195E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3523 | ambiguous | 0.3612 | ambiguous | -0.559 | Destabilizing | 0.998 | D | 0.605 | neutral | N | 0.472507647 | None | None | N |
| D/C | 0.8793 | likely_pathogenic | 0.8818 | pathogenic | -0.1 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| D/E | 0.392 | ambiguous | 0.3815 | ambiguous | -0.535 | Destabilizing | 0.91 | D | 0.397 | neutral | N | 0.504106782 | None | None | N |
| D/F | 0.8767 | likely_pathogenic | 0.8695 | pathogenic | -0.37 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| D/G | 0.3375 | likely_benign | 0.3468 | ambiguous | -0.828 | Destabilizing | 0.993 | D | 0.644 | neutral | N | 0.483067485 | None | None | N |
| D/H | 0.601 | likely_pathogenic | 0.6213 | pathogenic | -0.506 | Destabilizing | 0.836 | D | 0.407 | neutral | N | 0.499085053 | None | None | N |
| D/I | 0.8473 | likely_pathogenic | 0.8334 | pathogenic | 0.123 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/K | 0.7819 | likely_pathogenic | 0.7945 | pathogenic | 0.001 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/L | 0.7437 | likely_pathogenic | 0.74 | pathogenic | 0.123 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/M | 0.8871 | likely_pathogenic | 0.877 | pathogenic | 0.451 | Stabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| D/N | 0.2193 | likely_benign | 0.2191 | benign | -0.39 | Destabilizing | 0.996 | D | 0.653 | neutral | N | 0.515035852 | None | None | N |
| D/P | 0.9816 | likely_pathogenic | 0.9796 | pathogenic | -0.081 | Destabilizing | 0.995 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/Q | 0.6786 | likely_pathogenic | 0.6921 | pathogenic | -0.33 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/R | 0.7381 | likely_pathogenic | 0.7583 | pathogenic | 0.129 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| D/S | 0.2493 | likely_benign | 0.2519 | benign | -0.543 | Destabilizing | 0.996 | D | 0.654 | neutral | None | None | None | None | N |
| D/T | 0.5713 | likely_pathogenic | 0.5664 | pathogenic | -0.329 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| D/V | 0.6503 | likely_pathogenic | 0.6401 | pathogenic | -0.081 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | N | 0.495348843 | None | None | N |
| D/W | 0.9694 | likely_pathogenic | 0.9671 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| D/Y | 0.5771 | likely_pathogenic | 0.5837 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.499085053 | 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.