Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24925 | 74998;74999;75000 | chr2:178571359;178571358;178571357 | chr2:179436086;179436085;179436084 |
| N2AB | 23284 | 70075;70076;70077 | chr2:178571359;178571358;178571357 | chr2:179436086;179436085;179436084 |
| N2A | 22357 | 67294;67295;67296 | chr2:178571359;178571358;178571357 | chr2:179436086;179436085;179436084 |
| N2B | 15860 | 47803;47804;47805 | chr2:178571359;178571358;178571357 | chr2:179436086;179436085;179436084 |
| Novex-1 | 15985 | 48178;48179;48180 | chr2:178571359;178571358;178571357 | chr2:179436086;179436085;179436084 |
| Novex-2 | 16052 | 48379;48380;48381 | chr2:178571359;178571358;178571357 | chr2:179436086;179436085;179436084 |
| 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/L | None | None | 0.927 | N | 0.437 | 0.249 | 0.456552270603 | gnomAD-4.0.0 | 6.84349E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65722E-05 |
| M/T | None | None | 0.994 | N | 0.781 | 0.591 | 0.65604970179 | gnomAD-4.0.0 | 3.42173E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69882E-06 | 0 | 3.31455E-05 |
| M/V | None | None | 0.985 | N | 0.545 | 0.381 | 0.388812400583 | gnomAD-4.0.0 | 6.84349E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 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 | 0.7424 | likely_pathogenic | 0.7235 | pathogenic | -1.7 | Destabilizing | 0.989 | D | 0.702 | prob.neutral | None | None | None | None | N |
| M/C | 0.863 | likely_pathogenic | 0.8465 | pathogenic | -2.448 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| M/D | 0.9973 | likely_pathogenic | 0.9969 | pathogenic | -1.637 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| M/E | 0.9655 | likely_pathogenic | 0.9565 | pathogenic | -1.415 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| M/F | 0.742 | likely_pathogenic | 0.7354 | pathogenic | -0.592 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| M/G | 0.9597 | likely_pathogenic | 0.9598 | pathogenic | -2.162 | Highly Destabilizing | 0.995 | D | 0.76 | deleterious | None | None | None | None | N |
| M/H | 0.9811 | likely_pathogenic | 0.9765 | pathogenic | -1.971 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| M/I | 0.598 | likely_pathogenic | 0.6013 | pathogenic | -0.389 | Destabilizing | 0.985 | D | 0.657 | neutral | N | 0.42928095 | None | None | N |
| M/K | 0.9301 | likely_pathogenic | 0.9178 | pathogenic | -0.883 | Destabilizing | 0.994 | D | 0.782 | deleterious | N | 0.512781535 | None | None | N |
| M/L | 0.357 | ambiguous | 0.3548 | ambiguous | -0.389 | Destabilizing | 0.927 | D | 0.437 | neutral | N | 0.477375967 | None | None | N |
| M/N | 0.9802 | likely_pathogenic | 0.978 | pathogenic | -1.296 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| M/P | 0.9983 | likely_pathogenic | 0.998 | pathogenic | -0.806 | Destabilizing | 0.999 | D | 0.803 | deleterious | None | None | None | None | N |
| M/Q | 0.7986 | likely_pathogenic | 0.7663 | pathogenic | -0.989 | Destabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | None | N |
| M/R | 0.9179 | likely_pathogenic | 0.9047 | pathogenic | -1.151 | Destabilizing | 0.998 | D | 0.815 | deleterious | N | 0.501260645 | None | None | N |
| M/S | 0.8898 | likely_pathogenic | 0.8798 | pathogenic | -1.862 | Destabilizing | 0.995 | D | 0.761 | deleterious | None | None | None | None | N |
| M/T | 0.7687 | likely_pathogenic | 0.7551 | pathogenic | -1.498 | Destabilizing | 0.994 | D | 0.781 | deleterious | N | 0.489397361 | None | None | N |
| M/V | 0.1733 | likely_benign | 0.1633 | benign | -0.806 | Destabilizing | 0.985 | D | 0.545 | neutral | N | 0.414599499 | None | None | N |
| M/W | 0.9722 | likely_pathogenic | 0.9696 | pathogenic | -0.896 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| M/Y | 0.9669 | likely_pathogenic | 0.964 | pathogenic | -0.76 | Destabilizing | 0.999 | D | 0.825 | 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.