Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32974 | 99145;99146;99147 | chr2:178539015;178539014;178539013 | chr2:179403742;179403741;179403740 |
| N2AB | 31333 | 94222;94223;94224 | chr2:178539015;178539014;178539013 | chr2:179403742;179403741;179403740 |
| N2A | 30406 | 91441;91442;91443 | chr2:178539015;178539014;178539013 | chr2:179403742;179403741;179403740 |
| N2B | 23909 | 71950;71951;71952 | chr2:178539015;178539014;178539013 | chr2:179403742;179403741;179403740 |
| Novex-1 | 24034 | 72325;72326;72327 | chr2:178539015;178539014;178539013 | chr2:179403742;179403741;179403740 |
| Novex-2 | 24101 | 72526;72527;72528 | chr2:178539015;178539014;178539013 | chr2:179403742;179403741;179403740 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs374454949  |
-1.627 | 1.0 | D | 0.835 | 0.615 | None | gnomAD-2.1.1 | 4.02E-05 | None | None | None | None | N | None | 0 | 1.45003E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.56E-05 | 0 |
| A/T | rs374454949 |
-1.627 | 1.0 | D | 0.835 | 0.615 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/T | rs374454949 |
-1.627 | 1.0 | D | 0.835 | 0.615 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| A/T | rs374454949 |
-1.627 | 1.0 | D | 0.835 | 0.615 | None | gnomAD-4.0.0 | 3.28439E-05 | None | None | None | None | N | None | 0 | 6.66533E-05 | None | 0 | 2.22866E-05 | None | 0 | 0 | 3.47545E-05 | 3.29402E-05 | 6.40348E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.836 | likely_pathogenic | 0.7828 | pathogenic | -1.792 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| A/D | 0.9983 | likely_pathogenic | 0.9975 | pathogenic | -2.929 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| A/E | 0.9957 | likely_pathogenic | 0.9924 | pathogenic | -2.685 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.565065698 | None | None | N |
| A/F | 0.9889 | likely_pathogenic | 0.9791 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.951 | deleterious | None | None | None | None | N |
| A/G | 0.6443 | likely_pathogenic | 0.6545 | pathogenic | -2.329 | Highly Destabilizing | 1.0 | D | 0.687 | prob.neutral | D | 0.52784323 | None | None | N |
| A/H | 0.997 | likely_pathogenic | 0.9951 | pathogenic | -2.251 | Highly Destabilizing | 1.0 | D | 0.94 | deleterious | None | None | None | None | N |
| A/I | 0.9551 | likely_pathogenic | 0.9096 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| A/K | 0.9993 | likely_pathogenic | 0.9985 | pathogenic | -1.506 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| A/L | 0.896 | likely_pathogenic | 0.8382 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| A/M | 0.9638 | likely_pathogenic | 0.9383 | pathogenic | -1.118 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| A/N | 0.9929 | likely_pathogenic | 0.9888 | pathogenic | -1.986 | Destabilizing | 1.0 | D | 0.949 | deleterious | None | None | None | None | N |
| A/P | 0.9615 | likely_pathogenic | 0.9523 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.565319187 | None | None | N |
| A/Q | 0.9888 | likely_pathogenic | 0.9829 | pathogenic | -1.696 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| A/R | 0.995 | likely_pathogenic | 0.9909 | pathogenic | -1.597 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| A/S | 0.3458 | ambiguous | 0.3386 | benign | -2.359 | Highly Destabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.505406881 | None | None | N |
| A/T | 0.7411 | likely_pathogenic | 0.6209 | pathogenic | -2.003 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.561263355 | None | None | N |
| A/V | 0.7881 | likely_pathogenic | 0.6689 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.544933527 | None | None | N |
| A/W | 0.999 | likely_pathogenic | 0.9984 | pathogenic | -1.46 | Destabilizing | 1.0 | D | 0.929 | deleterious | None | None | None | None | N |
| A/Y | 0.9965 | likely_pathogenic | 0.9937 | pathogenic | -1.16 | Destabilizing | 1.0 | D | 0.951 | 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.