Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31744 | 95455;95456;95457 | chr2:178546006;178546005;178546004 | chr2:179410733;179410732;179410731 |
| N2AB | 30103 | 90532;90533;90534 | chr2:178546006;178546005;178546004 | chr2:179410733;179410732;179410731 |
| N2A | 29176 | 87751;87752;87753 | chr2:178546006;178546005;178546004 | chr2:179410733;179410732;179410731 |
| N2B | 22679 | 68260;68261;68262 | chr2:178546006;178546005;178546004 | chr2:179410733;179410732;179410731 |
| Novex-1 | 22804 | 68635;68636;68637 | chr2:178546006;178546005;178546004 | chr2:179410733;179410732;179410731 |
| Novex-2 | 22871 | 68836;68837;68838 | chr2:178546006;178546005;178546004 | chr2:179410733;179410732;179410731 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs749403545  |
-1.62 | 0.016 | N | 0.243 | 0.029 | 0.37208793 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/V | rs749403545 |
-1.62 | 0.016 | N | 0.243 | 0.029 | 0.37208793 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs749403545 |
-1.62 | 0.016 | N | 0.243 | 0.029 | 0.37208793 | gnomAD-4.0.0 | 9.29536E-06 | None | None | None | None | I | None | 2.66951E-05 | 1.66678E-05 | None | 0 | 0 | None | 0 | 0 | 1.01713E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3822 | ambiguous | 0.2899 | benign | -2.766 | Highly Destabilizing | 0.25 | N | 0.512 | neutral | None | None | None | None | I |
| I/C | 0.6898 | likely_pathogenic | 0.576 | pathogenic | -1.898 | Destabilizing | 0.992 | D | 0.592 | neutral | None | None | None | None | I |
| I/D | 0.8996 | likely_pathogenic | 0.8425 | pathogenic | -3.223 | Highly Destabilizing | 0.85 | D | 0.654 | neutral | None | None | None | None | I |
| I/E | 0.7541 | likely_pathogenic | 0.6607 | pathogenic | -3.052 | Highly Destabilizing | 0.85 | D | 0.657 | neutral | None | None | None | None | I |
| I/F | 0.2558 | likely_benign | 0.2085 | benign | -1.687 | Destabilizing | 0.681 | D | 0.555 | neutral | N | 0.47373542 | None | None | I |
| I/G | 0.8332 | likely_pathogenic | 0.749 | pathogenic | -3.232 | Highly Destabilizing | 0.85 | D | 0.658 | neutral | None | None | None | None | I |
| I/H | 0.6529 | likely_pathogenic | 0.5596 | ambiguous | -2.606 | Highly Destabilizing | 0.992 | D | 0.673 | neutral | None | None | None | None | I |
| I/K | 0.6425 | likely_pathogenic | 0.5442 | ambiguous | -2.289 | Highly Destabilizing | 0.85 | D | 0.658 | neutral | None | None | None | None | I |
| I/L | 0.1421 | likely_benign | 0.1121 | benign | -1.424 | Destabilizing | 0.002 | N | 0.262 | neutral | N | 0.5054536 | None | None | I |
| I/M | 0.1236 | likely_benign | 0.1003 | benign | -1.241 | Destabilizing | 0.916 | D | 0.576 | neutral | N | 0.504121 | None | None | I |
| I/N | 0.5407 | ambiguous | 0.4386 | ambiguous | -2.493 | Highly Destabilizing | 0.81 | D | 0.653 | neutral | N | 0.50726175 | None | None | I |
| I/P | 0.9831 | likely_pathogenic | 0.9714 | pathogenic | -1.855 | Destabilizing | 0.92 | D | 0.653 | neutral | None | None | None | None | I |
| I/Q | 0.6133 | likely_pathogenic | 0.4949 | ambiguous | -2.455 | Highly Destabilizing | 0.92 | D | 0.659 | neutral | None | None | None | None | I |
| I/R | 0.5059 | ambiguous | 0.4083 | ambiguous | -1.763 | Destabilizing | 0.85 | D | 0.663 | neutral | None | None | None | None | I |
| I/S | 0.4005 | ambiguous | 0.3149 | benign | -3.092 | Highly Destabilizing | 0.379 | N | 0.586 | neutral | N | 0.47069353 | None | None | I |
| I/T | 0.1573 | likely_benign | 0.1131 | benign | -2.81 | Highly Destabilizing | 0.004 | N | 0.445 | neutral | N | 0.4668579 | None | None | I |
| I/V | 0.071 | likely_benign | 0.0669 | benign | -1.855 | Destabilizing | 0.016 | N | 0.243 | neutral | N | 0.4266088 | None | None | I |
| I/W | 0.7959 | likely_pathogenic | 0.7587 | pathogenic | -2.095 | Highly Destabilizing | 0.992 | D | 0.69 | prob.neutral | None | None | None | None | I |
| I/Y | 0.6048 | likely_pathogenic | 0.5355 | ambiguous | -1.886 | Destabilizing | 0.92 | D | 0.599 | neutral | None | None | None | None | I |
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.