Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33395 | 100408;100409;100410 | chr2:178536564;178536563;178536562 | chr2:179401291;179401290;179401289 |
| N2AB | 31754 | 95485;95486;95487 | chr2:178536564;178536563;178536562 | chr2:179401291;179401290;179401289 |
| N2A | 30827 | 92704;92705;92706 | chr2:178536564;178536563;178536562 | chr2:179401291;179401290;179401289 |
| N2B | 24330 | 73213;73214;73215 | chr2:178536564;178536563;178536562 | chr2:179401291;179401290;179401289 |
| Novex-1 | 24455 | 73588;73589;73590 | chr2:178536564;178536563;178536562 | chr2:179401291;179401290;179401289 |
| Novex-2 | 24522 | 73789;73790;73791 | chr2:178536564;178536563;178536562 | chr2:179401291;179401290;179401289 |
| 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 | rs761311859  |
None | 0.295 | N | 0.769 | 0.158 | 0.152612264143 | gnomAD-4.0.0 | 2.23571E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.88724E-06 | 0 | 1.8074E-05 |
| A/T | rs761311859 |
None | None | N | 0.371 | 0.174 | 0.144782658237 | gnomAD-4.0.0 | 2.98095E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.77448E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3963 | ambiguous | 0.3563 | ambiguous | -1.059 | Destabilizing | 0.676 | D | 0.655 | neutral | None | None | None | None | N |
| A/D | 0.3052 | likely_benign | 0.3246 | benign | -1.457 | Destabilizing | 0.055 | N | 0.788 | deleterious | N | 0.518157721 | None | None | N |
| A/E | 0.1736 | likely_benign | 0.18 | benign | -1.575 | Destabilizing | 0.038 | N | 0.689 | prob.neutral | None | None | None | None | N |
| A/F | 0.2214 | likely_benign | 0.2288 | benign | -1.4 | Destabilizing | 0.214 | N | 0.785 | deleterious | None | None | None | None | N |
| A/G | 0.1725 | likely_benign | 0.1645 | benign | -0.921 | Destabilizing | 0.055 | N | 0.621 | neutral | N | 0.507054905 | None | None | N |
| A/H | 0.3558 | ambiguous | 0.3648 | ambiguous | -0.879 | Destabilizing | 0.676 | D | 0.821 | deleterious | None | None | None | None | N |
| A/I | 0.1114 | likely_benign | 0.1029 | benign | -0.693 | Destabilizing | None | N | 0.463 | neutral | None | None | None | None | N |
| A/K | 0.2275 | likely_benign | 0.2797 | benign | -0.931 | Destabilizing | 0.038 | N | 0.681 | prob.neutral | None | None | None | None | N |
| A/L | 0.1063 | likely_benign | 0.102 | benign | -0.693 | Destabilizing | 0.007 | N | 0.573 | neutral | None | None | None | None | N |
| A/M | 0.1516 | likely_benign | 0.1355 | benign | -0.493 | Destabilizing | 0.007 | N | 0.567 | neutral | None | None | None | None | N |
| A/N | 0.2123 | likely_benign | 0.2047 | benign | -0.726 | Destabilizing | 0.214 | N | 0.795 | deleterious | None | None | None | None | N |
| A/P | 0.0966 | likely_benign | 0.0909 | benign | -0.7 | Destabilizing | 0.295 | N | 0.769 | deleterious | N | 0.438964799 | None | None | N |
| A/Q | 0.1863 | likely_benign | 0.1887 | benign | -1.093 | Destabilizing | 0.002 | N | 0.525 | neutral | None | None | None | None | N |
| A/R | 0.22 | likely_benign | 0.2783 | benign | -0.424 | Destabilizing | 0.12 | N | 0.767 | deleterious | None | None | None | None | N |
| A/S | 0.0949 | likely_benign | 0.0915 | benign | -0.932 | Destabilizing | 0.012 | N | 0.604 | neutral | D | 0.522660831 | None | None | N |
| A/T | 0.0801 | likely_benign | 0.0764 | benign | -0.985 | Destabilizing | None | N | 0.371 | neutral | N | 0.483924221 | None | None | N |
| A/V | 0.0788 | likely_benign | 0.0757 | benign | -0.7 | Destabilizing | None | N | 0.321 | neutral | N | 0.476024182 | None | None | N |
| A/W | 0.6822 | likely_pathogenic | 0.7076 | pathogenic | -1.522 | Destabilizing | 0.864 | D | 0.823 | deleterious | None | None | None | None | N |
| A/Y | 0.3691 | ambiguous | 0.3714 | ambiguous | -1.159 | Destabilizing | 0.356 | N | 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.