Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32239 | 96940;96941;96942 | chr2:178543258;178543257;178543256 | chr2:179407985;179407984;179407983 |
| N2AB | 30598 | 92017;92018;92019 | chr2:178543258;178543257;178543256 | chr2:179407985;179407984;179407983 |
| N2A | 29671 | 89236;89237;89238 | chr2:178543258;178543257;178543256 | chr2:179407985;179407984;179407983 |
| N2B | 23174 | 69745;69746;69747 | chr2:178543258;178543257;178543256 | chr2:179407985;179407984;179407983 |
| Novex-1 | 23299 | 70120;70121;70122 | chr2:178543258;178543257;178543256 | chr2:179407985;179407984;179407983 |
| Novex-2 | 23366 | 70321;70322;70323 | chr2:178543258;178543257;178543256 | chr2:179407985;179407984;179407983 |
| 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/F | rs889392294  |
-1.815 | 0.982 | N | 0.647 | 0.337 | 0.708166648873 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs889392294 |
-1.815 | 0.982 | N | 0.647 | 0.337 | 0.708166648873 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs889392294 |
-1.815 | 0.982 | N | 0.647 | 0.337 | 0.708166648873 | gnomAD-4.0.0 | 3.84352E-06 | None | None | None | None | N | None | 0 | 3.39098E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84398E-05 |
| L/P | None | None | 0.997 | N | 0.891 | 0.604 | 0.864429176489 | gnomAD-4.0.0 | 4.10511E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39674E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6857 | likely_pathogenic | 0.6756 | pathogenic | -3.214 | Highly Destabilizing | 0.953 | D | 0.663 | neutral | None | None | None | None | N |
| L/C | 0.8458 | likely_pathogenic | 0.8393 | pathogenic | -2.452 | Highly Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| L/D | 0.9984 | likely_pathogenic | 0.9984 | pathogenic | -3.931 | Highly Destabilizing | 0.998 | D | 0.888 | deleterious | None | None | None | None | N |
| L/E | 0.9891 | likely_pathogenic | 0.9888 | pathogenic | -3.619 | Highly Destabilizing | 0.998 | D | 0.877 | deleterious | None | None | None | None | N |
| L/F | 0.6363 | likely_pathogenic | 0.6014 | pathogenic | -1.925 | Destabilizing | 0.982 | D | 0.647 | neutral | N | 0.482478963 | None | None | N |
| L/G | 0.9614 | likely_pathogenic | 0.9614 | pathogenic | -3.787 | Highly Destabilizing | 0.998 | D | 0.872 | deleterious | None | None | None | None | N |
| L/H | 0.9843 | likely_pathogenic | 0.9832 | pathogenic | -3.315 | Highly Destabilizing | 0.999 | D | 0.863 | deleterious | N | 0.482732452 | None | None | N |
| L/I | 0.0962 | likely_benign | 0.0924 | benign | -1.465 | Destabilizing | 0.02 | N | 0.267 | neutral | N | 0.334983922 | None | None | N |
| L/K | 0.9849 | likely_pathogenic | 0.9865 | pathogenic | -2.666 | Highly Destabilizing | 0.993 | D | 0.843 | deleterious | None | None | None | None | N |
| L/M | 0.2167 | likely_benign | 0.2123 | benign | -1.651 | Destabilizing | 0.986 | D | 0.612 | neutral | None | None | None | None | N |
| L/N | 0.9915 | likely_pathogenic | 0.9919 | pathogenic | -3.388 | Highly Destabilizing | 0.998 | D | 0.89 | deleterious | None | None | None | None | N |
| L/P | 0.9801 | likely_pathogenic | 0.9792 | pathogenic | -2.044 | Highly Destabilizing | 0.997 | D | 0.891 | deleterious | N | 0.482732452 | None | None | N |
| L/Q | 0.9655 | likely_pathogenic | 0.9649 | pathogenic | -3.063 | Highly Destabilizing | 0.998 | D | 0.875 | deleterious | None | None | None | None | N |
| L/R | 0.9753 | likely_pathogenic | 0.9746 | pathogenic | -2.569 | Highly Destabilizing | 0.997 | D | 0.863 | deleterious | N | 0.482732452 | None | None | N |
| L/S | 0.9657 | likely_pathogenic | 0.9612 | pathogenic | -3.901 | Highly Destabilizing | 0.993 | D | 0.829 | deleterious | None | None | None | None | N |
| L/T | 0.7933 | likely_pathogenic | 0.7838 | pathogenic | -3.44 | Highly Destabilizing | 0.986 | D | 0.726 | prob.delet. | None | None | None | None | N |
| L/V | 0.1098 | likely_benign | 0.0991 | benign | -2.044 | Highly Destabilizing | 0.76 | D | 0.383 | neutral | N | 0.363434386 | None | None | N |
| L/W | 0.9425 | likely_pathogenic | 0.9391 | pathogenic | -2.287 | Highly Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| L/Y | 0.9675 | likely_pathogenic | 0.963 | pathogenic | -2.196 | Highly Destabilizing | 0.998 | D | 0.737 | prob.delet. | 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.