Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22820 | 68683;68684;68685 | chr2:178578057;178578056;178578055 | chr2:179442784;179442783;179442782 |
| N2AB | 21179 | 63760;63761;63762 | chr2:178578057;178578056;178578055 | chr2:179442784;179442783;179442782 |
| N2A | 20252 | 60979;60980;60981 | chr2:178578057;178578056;178578055 | chr2:179442784;179442783;179442782 |
| N2B | 13755 | 41488;41489;41490 | chr2:178578057;178578056;178578055 | chr2:179442784;179442783;179442782 |
| Novex-1 | 13880 | 41863;41864;41865 | chr2:178578057;178578056;178578055 | chr2:179442784;179442783;179442782 |
| Novex-2 | 13947 | 42064;42065;42066 | chr2:178578057;178578056;178578055 | chr2:179442784;179442783;179442782 |
| 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/P | rs72646880  |
-0.908 | 1.0 | D | 0.882 | 0.761 | None | gnomAD-2.1.1 | 1.83585E-03 | None | None | None | None | N | None | 2.4818E-04 | 7.07574E-04 | None | 5.32636E-03 | 0 | None | 2.77887E-03 | None | 2.79955E-04 | 2.45432E-03 | 3.09685E-03 |
| A/P | rs72646880 |
-0.908 | 1.0 | D | 0.882 | 0.761 | None | gnomAD-3.1.2 | 1.58488E-03 | None | None | None | None | N | None | 3.62056E-04 | 8.52795E-04 | 0 | 5.47866E-03 | 0 | None | 3.76861E-04 | 6.32911E-03 | 2.51537E-03 | 2.48447E-03 | 2.39006E-03 |
| A/P | rs72646880 |
-0.908 | 1.0 | D | 0.882 | 0.761 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 2.9E-03 | None | None | 0 | 1E-03 | None | None | None | 1E-03 | None |
| A/P | rs72646880 |
-0.908 | 1.0 | D | 0.882 | 0.761 | None | gnomAD-4.0.0 | 1.86089E-03 | None | None | None | None | N | None | 4.66766E-04 | 7.83595E-04 | None | 6.59229E-03 | 0 | None | 3.43836E-04 | 4.29468E-03 | 1.92884E-03 | 2.72396E-03 | 2.46574E-03 |
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 | 0.9064 | likely_pathogenic | 0.8772 | pathogenic | -1.714 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| A/D | 0.9964 | likely_pathogenic | 0.9979 | pathogenic | -2.94 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| A/E | 0.9961 | likely_pathogenic | 0.9974 | pathogenic | -2.695 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.66035977 | None | None | N |
| A/F | 0.9952 | likely_pathogenic | 0.9965 | pathogenic | -0.782 | Destabilizing | 1.0 | D | 0.927 | deleterious | None | None | None | None | N |
| A/G | 0.4552 | ambiguous | 0.4633 | ambiguous | -2.21 | Highly Destabilizing | 1.0 | D | 0.596 | neutral | D | 0.587208262 | None | None | N |
| A/H | 0.998 | likely_pathogenic | 0.9984 | pathogenic | -2.263 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| A/I | 0.9889 | likely_pathogenic | 0.9883 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| A/K | 0.9993 | likely_pathogenic | 0.9995 | pathogenic | -1.486 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/L | 0.9537 | likely_pathogenic | 0.9552 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| A/M | 0.9783 | likely_pathogenic | 0.9787 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| A/N | 0.9906 | likely_pathogenic | 0.9926 | pathogenic | -1.963 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| A/P | 0.9701 | likely_pathogenic | 0.9538 | pathogenic | -0.863 | Destabilizing | 1.0 | D | 0.882 | deleterious | D | 0.618398689 | None | None | N |
| A/Q | 0.9936 | likely_pathogenic | 0.9945 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| A/R | 0.9963 | likely_pathogenic | 0.9973 | pathogenic | -1.591 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| A/S | 0.4532 | ambiguous | 0.4704 | ambiguous | -2.319 | Highly Destabilizing | 1.0 | D | 0.583 | neutral | D | 0.604943857 | None | None | N |
| A/T | 0.8747 | likely_pathogenic | 0.8923 | pathogenic | -1.963 | Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.634014441 | None | None | N |
| A/V | 0.9117 | likely_pathogenic | 0.9144 | pathogenic | -0.863 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.642927779 | None | None | N |
| A/W | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.478 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| A/Y | 0.9979 | likely_pathogenic | 0.9983 | pathogenic | -1.127 | Destabilizing | 1.0 | D | 0.926 | 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.