Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18386 | 55381;55382;55383 | chr2:178602115;178602114;178602113 | chr2:179466842;179466841;179466840 |
| N2AB | 16745 | 50458;50459;50460 | chr2:178602115;178602114;178602113 | chr2:179466842;179466841;179466840 |
| N2A | 15818 | 47677;47678;47679 | chr2:178602115;178602114;178602113 | chr2:179466842;179466841;179466840 |
| N2B | 9321 | 28186;28187;28188 | chr2:178602115;178602114;178602113 | chr2:179466842;179466841;179466840 |
| Novex-1 | 9446 | 28561;28562;28563 | chr2:178602115;178602114;178602113 | chr2:179466842;179466841;179466840 |
| Novex-2 | 9513 | 28762;28763;28764 | chr2:178602115;178602114;178602113 | chr2:179466842;179466841;179466840 |
| 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/E | rs1368488104  |
-0.448 | 0.619 | N | 0.367 | 0.084 | 0.119812018005 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.63E-05 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs1368488104 |
-0.448 | 0.619 | N | 0.367 | 0.084 | 0.119812018005 | gnomAD-4.0.0 | 1.59672E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78536E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | None | None | 1.0 | N | 0.777 | 0.424 | 0.418344901717 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.17284E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3878 | ambiguous | 0.3886 | ambiguous | 0.103 | Stabilizing | 0.998 | D | 0.715 | prob.delet. | N | 0.486854418 | None | None | N |
| D/C | 0.8589 | likely_pathogenic | 0.8631 | pathogenic | 0.127 | Stabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| D/E | 0.2124 | likely_benign | 0.1909 | benign | -0.123 | Destabilizing | 0.619 | D | 0.367 | neutral | N | 0.455515906 | None | None | N |
| D/F | 0.838 | likely_pathogenic | 0.8482 | pathogenic | -0.052 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| D/G | 0.3117 | likely_benign | 0.311 | benign | -0.017 | Destabilizing | 0.996 | D | 0.693 | prob.neutral | N | 0.517721945 | None | None | N |
| D/H | 0.5916 | likely_pathogenic | 0.6076 | pathogenic | 0.368 | Stabilizing | 1.0 | D | 0.777 | deleterious | N | 0.488121865 | None | None | N |
| D/I | 0.6979 | likely_pathogenic | 0.706 | pathogenic | 0.348 | Stabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| D/K | 0.6766 | likely_pathogenic | 0.675 | pathogenic | 0.56 | Stabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/L | 0.7066 | likely_pathogenic | 0.7151 | pathogenic | 0.348 | Stabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| D/M | 0.8465 | likely_pathogenic | 0.8407 | pathogenic | 0.25 | Stabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| D/N | 0.2062 | likely_benign | 0.1921 | benign | 0.448 | Stabilizing | 0.999 | D | 0.645 | neutral | N | 0.465943544 | None | None | N |
| D/P | 0.8095 | likely_pathogenic | 0.8009 | pathogenic | 0.286 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/Q | 0.5768 | likely_pathogenic | 0.5699 | pathogenic | 0.441 | Stabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/R | 0.7134 | likely_pathogenic | 0.7278 | pathogenic | 0.687 | Stabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| D/S | 0.2912 | likely_benign | 0.2715 | benign | 0.324 | Stabilizing | 0.994 | D | 0.614 | neutral | None | None | None | None | N |
| D/T | 0.4738 | ambiguous | 0.4529 | ambiguous | 0.416 | Stabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| D/V | 0.482 | ambiguous | 0.508 | ambiguous | 0.286 | Stabilizing | 0.999 | D | 0.804 | deleterious | N | 0.488121865 | None | None | N |
| D/W | 0.9512 | likely_pathogenic | 0.956 | pathogenic | -0.038 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| D/Y | 0.4864 | ambiguous | 0.5083 | ambiguous | 0.171 | Stabilizing | 1.0 | D | 0.836 | deleterious | N | 0.488628844 | 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.