Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14490 | 43693;43694;43695 | chr2:178632538;178632537;178632536 | chr2:179497265;179497264;179497263 |
| N2AB | 12849 | 38770;38771;38772 | chr2:178632538;178632537;178632536 | chr2:179497265;179497264;179497263 |
| N2A | 11922 | 35989;35990;35991 | chr2:178632538;178632537;178632536 | chr2:179497265;179497264;179497263 |
| N2B | 5425 | 16498;16499;16500 | chr2:178632538;178632537;178632536 | chr2:179497265;179497264;179497263 |
| Novex-1 | 5550 | 16873;16874;16875 | chr2:178632538;178632537;178632536 | chr2:179497265;179497264;179497263 |
| Novex-2 | 5617 | 17074;17075;17076 | chr2:178632538;178632537;178632536 | chr2:179497265;179497264;179497263 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/R | rs2154221765  |
None | 1.0 | D | 0.815 | 0.799 | 0.911696079222 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | rs2154221765 |
None | 1.0 | D | 0.815 | 0.799 | 0.911696079222 | gnomAD-4.0.0 | 6.56797E-06 | None | None | None | None | N | None | 2.40431E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9624 | likely_pathogenic | 0.9602 | pathogenic | -2.947 | Highly Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| L/C | 0.9466 | likely_pathogenic | 0.9341 | pathogenic | -1.923 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -3.628 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| L/E | 0.9966 | likely_pathogenic | 0.9971 | pathogenic | -3.327 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| L/F | 0.8792 | likely_pathogenic | 0.8237 | pathogenic | -1.798 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| L/G | 0.9915 | likely_pathogenic | 0.9916 | pathogenic | -3.523 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| L/H | 0.9943 | likely_pathogenic | 0.9937 | pathogenic | -3.118 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/I | 0.3749 | ambiguous | 0.2999 | benign | -1.212 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| L/K | 0.9944 | likely_pathogenic | 0.995 | pathogenic | -2.309 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/M | 0.5036 | ambiguous | 0.4409 | ambiguous | -1.195 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.71492724 | None | None | N |
| L/N | 0.9953 | likely_pathogenic | 0.9964 | pathogenic | -2.951 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/P | 0.9978 | likely_pathogenic | 0.9976 | pathogenic | -1.782 | Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.714111544 | None | None | N |
| L/Q | 0.9898 | likely_pathogenic | 0.9905 | pathogenic | -2.659 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.714034754 | None | None | N |
| L/R | 0.9886 | likely_pathogenic | 0.9884 | pathogenic | -2.187 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.714034754 | None | None | N |
| L/S | 0.996 | likely_pathogenic | 0.9962 | pathogenic | -3.5 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/T | 0.9816 | likely_pathogenic | 0.9799 | pathogenic | -3.054 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/V | 0.4506 | ambiguous | 0.3603 | ambiguous | -1.782 | Destabilizing | 0.999 | D | 0.579 | neutral | D | 0.658469024 | None | None | N |
| L/W | 0.9867 | likely_pathogenic | 0.9807 | pathogenic | -2.258 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| L/Y | 0.9865 | likely_pathogenic | 0.9823 | pathogenic | -2.039 | Highly Destabilizing | 1.0 | D | 0.815 | 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.