Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23757 | 71494;71495;71496 | chr2:178574863;178574862;178574861 | chr2:179439590;179439589;179439588 |
| N2AB | 22116 | 66571;66572;66573 | chr2:178574863;178574862;178574861 | chr2:179439590;179439589;179439588 |
| N2A | 21189 | 63790;63791;63792 | chr2:178574863;178574862;178574861 | chr2:179439590;179439589;179439588 |
| N2B | 14692 | 44299;44300;44301 | chr2:178574863;178574862;178574861 | chr2:179439590;179439589;179439588 |
| Novex-1 | 14817 | 44674;44675;44676 | chr2:178574863;178574862;178574861 | chr2:179439590;179439589;179439588 |
| Novex-2 | 14884 | 44875;44876;44877 | chr2:178574863;178574862;178574861 | chr2:179439590;179439589;179439588 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs767128219  |
None | 0.63 | N | 0.61 | 0.254 | 0.452072420954 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs767128219 |
None | 0.63 | N | 0.61 | 0.254 | 0.452072420954 | gnomAD-4.0.0 | 3.09992E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23885E-06 | 0 | 0 |
| V/G | rs767128219 |
-2.291 | 0.805 | N | 0.72 | 0.303 | 0.586724321019 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.69338E-04 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1387996821 |
-0.791 | 0.873 | N | 0.603 | 0.188 | 0.451692371253 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9E-06 | 0 |
| V/I | rs1387996821 |
-0.791 | 0.873 | N | 0.603 | 0.188 | 0.451692371253 | gnomAD-4.0.0 | 3.4226E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49819E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.5746 | likely_pathogenic | 0.4351 | ambiguous | -1.444 | Destabilizing | 0.63 | D | 0.61 | neutral | N | 0.365309616 | None | None | I |
| V/C | 0.8453 | likely_pathogenic | 0.7776 | pathogenic | -0.864 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | I |
| V/D | 0.9461 | likely_pathogenic | 0.9275 | pathogenic | -1.06 | Destabilizing | 0.975 | D | 0.751 | deleterious | None | None | None | None | I |
| V/E | 0.9091 | likely_pathogenic | 0.8766 | pathogenic | -1.054 | Destabilizing | 0.967 | D | 0.689 | prob.neutral | N | 0.452120524 | None | None | I |
| V/F | 0.5984 | likely_pathogenic | 0.4831 | ambiguous | -1.163 | Destabilizing | 0.987 | D | 0.675 | prob.neutral | None | None | None | None | I |
| V/G | 0.6865 | likely_pathogenic | 0.5779 | pathogenic | -1.771 | Destabilizing | 0.805 | D | 0.72 | prob.delet. | N | 0.429200805 | None | None | I |
| V/H | 0.9636 | likely_pathogenic | 0.9409 | pathogenic | -1.369 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | I |
| V/I | 0.1445 | likely_benign | 0.1163 | benign | -0.647 | Destabilizing | 0.873 | D | 0.603 | neutral | N | 0.47039964 | None | None | I |
| V/K | 0.9546 | likely_pathogenic | 0.9329 | pathogenic | -1.074 | Destabilizing | 0.975 | D | 0.693 | prob.neutral | None | None | None | None | I |
| V/L | 0.6767 | likely_pathogenic | 0.5319 | ambiguous | -0.647 | Destabilizing | 0.773 | D | 0.612 | neutral | N | 0.444175831 | None | None | I |
| V/M | 0.4579 | ambiguous | 0.3265 | benign | -0.444 | Destabilizing | 0.996 | D | 0.692 | prob.neutral | None | None | None | None | I |
| V/N | 0.7974 | likely_pathogenic | 0.7153 | pathogenic | -0.83 | Destabilizing | 0.975 | D | 0.743 | deleterious | None | None | None | None | I |
| V/P | 0.9892 | likely_pathogenic | 0.9859 | pathogenic | -0.877 | Destabilizing | 0.987 | D | 0.708 | prob.delet. | None | None | None | None | I |
| V/Q | 0.8876 | likely_pathogenic | 0.8353 | pathogenic | -0.976 | Destabilizing | 0.975 | D | 0.72 | prob.delet. | None | None | None | None | I |
| V/R | 0.9386 | likely_pathogenic | 0.9121 | pathogenic | -0.622 | Destabilizing | 0.975 | D | 0.755 | deleterious | None | None | None | None | I |
| V/S | 0.5076 | ambiguous | 0.4046 | ambiguous | -1.385 | Destabilizing | 0.253 | N | 0.565 | neutral | None | None | None | None | I |
| V/T | 0.5334 | ambiguous | 0.4101 | ambiguous | -1.262 | Destabilizing | 0.845 | D | 0.607 | neutral | None | None | None | None | I |
| V/W | 0.9914 | likely_pathogenic | 0.9831 | pathogenic | -1.365 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | I |
| V/Y | 0.9369 | likely_pathogenic | 0.9014 | pathogenic | -1.057 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | I |
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.