Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31425 | 94498;94499;94500 | chr2:178547252;178547251;178547250 | chr2:179411979;179411978;179411977 |
| N2AB | 29784 | 89575;89576;89577 | chr2:178547252;178547251;178547250 | chr2:179411979;179411978;179411977 |
| N2A | 28857 | 86794;86795;86796 | chr2:178547252;178547251;178547250 | chr2:179411979;179411978;179411977 |
| N2B | 22360 | 67303;67304;67305 | chr2:178547252;178547251;178547250 | chr2:179411979;179411978;179411977 |
| Novex-1 | 22485 | 67678;67679;67680 | chr2:178547252;178547251;178547250 | chr2:179411979;179411978;179411977 |
| Novex-2 | 22552 | 67879;67880;67881 | chr2:178547252;178547251;178547250 | chr2:179411979;179411978;179411977 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.001 | N | 0.251 | 0.135 | 0.434606191737 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/K | rs764947983  |
-1.066 | 0.784 | N | 0.725 | 0.502 | 0.695986974221 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 9.19118E-04 |
| M/K | rs764947983 |
-1.066 | 0.784 | N | 0.725 | 0.502 | 0.695986974221 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/K | rs764947983 |
-1.066 | 0.784 | N | 0.725 | 0.502 | 0.695986974221 | gnomAD-4.0.0 | 2.56218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78652E-06 | 0 | 0 |
| M/T | rs764947983 |
-1.723 | 0.642 | N | 0.7 | 0.445 | 0.691146523942 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| M/T | rs764947983 |
-1.723 | 0.642 | N | 0.7 | 0.445 | 0.691146523942 | gnomAD-4.0.0 | 1.59138E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85865E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6788 | likely_pathogenic | 0.6908 | pathogenic | -1.94 | Destabilizing | 0.495 | N | 0.568 | neutral | None | None | None | None | N |
| M/C | 0.8814 | likely_pathogenic | 0.8689 | pathogenic | -2.294 | Highly Destabilizing | 0.981 | D | 0.766 | deleterious | None | None | None | None | N |
| M/D | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -2.106 | Highly Destabilizing | 0.981 | D | 0.786 | deleterious | None | None | None | None | N |
| M/E | 0.9925 | likely_pathogenic | 0.993 | pathogenic | -1.827 | Destabilizing | 0.936 | D | 0.742 | deleterious | None | None | None | None | N |
| M/F | 0.8354 | likely_pathogenic | 0.8324 | pathogenic | -0.44 | Destabilizing | 0.704 | D | 0.651 | neutral | None | None | None | None | N |
| M/G | 0.9733 | likely_pathogenic | 0.9742 | pathogenic | -2.46 | Highly Destabilizing | 0.936 | D | 0.737 | prob.delet. | None | None | None | None | N |
| M/H | 0.9961 | likely_pathogenic | 0.9966 | pathogenic | -2.362 | Highly Destabilizing | 0.995 | D | 0.751 | deleterious | None | None | None | None | N |
| M/I | 0.4662 | ambiguous | 0.4746 | ambiguous | -0.429 | Destabilizing | 0.001 | N | 0.251 | neutral | N | 0.443556969 | None | None | N |
| M/K | 0.9851 | likely_pathogenic | 0.9865 | pathogenic | -1.186 | Destabilizing | 0.784 | D | 0.725 | prob.delet. | N | 0.506856506 | None | None | N |
| M/L | 0.3735 | ambiguous | 0.3928 | ambiguous | -0.429 | Destabilizing | 0.065 | N | 0.318 | neutral | N | 0.486534168 | None | None | N |
| M/N | 0.9908 | likely_pathogenic | 0.992 | pathogenic | -1.738 | Destabilizing | 0.981 | D | 0.779 | deleterious | None | None | None | None | N |
| M/P | 0.9986 | likely_pathogenic | 0.9989 | pathogenic | -0.917 | Destabilizing | 0.981 | D | 0.779 | deleterious | None | None | None | None | N |
| M/Q | 0.9434 | likely_pathogenic | 0.9462 | pathogenic | -1.288 | Destabilizing | 0.981 | D | 0.726 | prob.delet. | None | None | None | None | N |
| M/R | 0.9829 | likely_pathogenic | 0.9857 | pathogenic | -1.585 | Destabilizing | 0.975 | D | 0.803 | deleterious | N | 0.506856506 | None | None | N |
| M/S | 0.9141 | likely_pathogenic | 0.9217 | pathogenic | -2.215 | Highly Destabilizing | 0.828 | D | 0.701 | prob.neutral | None | None | None | None | N |
| M/T | 0.8825 | likely_pathogenic | 0.884 | pathogenic | -1.792 | Destabilizing | 0.642 | D | 0.7 | prob.neutral | N | 0.488245272 | None | None | N |
| M/V | 0.1285 | likely_benign | 0.1306 | benign | -0.917 | Destabilizing | 0.065 | N | 0.409 | neutral | N | 0.429952953 | None | None | N |
| M/W | 0.9969 | likely_pathogenic | 0.9968 | pathogenic | -0.862 | Destabilizing | 0.995 | D | 0.745 | deleterious | None | None | None | None | N |
| M/Y | 0.9917 | likely_pathogenic | 0.9916 | pathogenic | -0.801 | Destabilizing | 0.981 | D | 0.807 | 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.