Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14518 | 43777;43778;43779 | chr2:178632342;178632341;178632340 | chr2:179497069;179497068;179497067 |
| N2AB | 12877 | 38854;38855;38856 | chr2:178632342;178632341;178632340 | chr2:179497069;179497068;179497067 |
| N2A | 11950 | 36073;36074;36075 | chr2:178632342;178632341;178632340 | chr2:179497069;179497068;179497067 |
| N2B | 5453 | 16582;16583;16584 | chr2:178632342;178632341;178632340 | chr2:179497069;179497068;179497067 |
| Novex-1 | 5578 | 16957;16958;16959 | chr2:178632342;178632341;178632340 | chr2:179497069;179497068;179497067 |
| Novex-2 | 5645 | 17158;17159;17160 | chr2:178632342;178632341;178632340 | chr2:179497069;179497068;179497067 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs746989081  |
-0.697 | 0.896 | D | 0.653 | 0.488 | 0.735016723692 | gnomAD-2.1.1 | 1.28E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.1966E-04 | None | 0 | None | 0 | 9.52E-06 | 0 |
| V/M | rs746989081 |
-0.697 | 0.896 | D | 0.653 | 0.488 | 0.735016723692 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs746989081 |
-0.697 | 0.896 | D | 0.653 | 0.488 | 0.735016723692 | gnomAD-4.0.0 | 4.36051E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.76072E-05 | None | 0 | 1.64908E-04 | 2.55186E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2753 | likely_benign | 0.2052 | benign | -2.021 | Highly Destabilizing | 0.002 | N | 0.356 | neutral | D | 0.530070741 | None | None | N |
| V/C | 0.8504 | likely_pathogenic | 0.8166 | pathogenic | -1.733 | Destabilizing | 0.977 | D | 0.769 | deleterious | None | None | None | None | N |
| V/D | 0.9845 | likely_pathogenic | 0.9773 | pathogenic | -3.077 | Highly Destabilizing | 0.85 | D | 0.803 | deleterious | None | None | None | None | N |
| V/E | 0.9653 | likely_pathogenic | 0.9536 | pathogenic | -2.774 | Highly Destabilizing | 0.549 | D | 0.787 | deleterious | D | 0.572346542 | None | None | N |
| V/F | 0.7453 | likely_pathogenic | 0.7137 | pathogenic | -1.05 | Destabilizing | 0.92 | D | 0.78 | deleterious | None | None | None | None | N |
| V/G | 0.6634 | likely_pathogenic | 0.5869 | pathogenic | -2.635 | Highly Destabilizing | 0.379 | N | 0.775 | deleterious | D | 0.572200211 | None | None | N |
| V/H | 0.9916 | likely_pathogenic | 0.9875 | pathogenic | -2.658 | Highly Destabilizing | 0.992 | D | 0.825 | deleterious | None | None | None | None | N |
| V/I | 0.1401 | likely_benign | 0.1419 | benign | -0.253 | Destabilizing | 0.009 | N | 0.374 | neutral | None | None | None | None | N |
| V/K | 0.9808 | likely_pathogenic | 0.9744 | pathogenic | -1.596 | Destabilizing | 0.617 | D | 0.789 | deleterious | None | None | None | None | N |
| V/L | 0.6183 | likely_pathogenic | 0.5836 | pathogenic | -0.253 | Destabilizing | 0.201 | N | 0.525 | neutral | N | 0.467666449 | None | None | N |
| V/M | 0.4518 | ambiguous | 0.4158 | ambiguous | -0.611 | Destabilizing | 0.896 | D | 0.653 | neutral | D | 0.572346542 | None | None | N |
| V/N | 0.9556 | likely_pathogenic | 0.9344 | pathogenic | -2.215 | Highly Destabilizing | 0.85 | D | 0.818 | deleterious | None | None | None | None | N |
| V/P | 0.9921 | likely_pathogenic | 0.9868 | pathogenic | -0.821 | Destabilizing | 0.92 | D | 0.792 | deleterious | None | None | None | None | N |
| V/Q | 0.9656 | likely_pathogenic | 0.9523 | pathogenic | -1.874 | Destabilizing | 0.92 | D | 0.809 | deleterious | None | None | None | None | N |
| V/R | 0.9625 | likely_pathogenic | 0.9506 | pathogenic | -1.737 | Destabilizing | 0.85 | D | 0.817 | deleterious | None | None | None | None | N |
| V/S | 0.663 | likely_pathogenic | 0.5713 | pathogenic | -2.758 | Highly Destabilizing | 0.447 | N | 0.741 | deleterious | None | None | None | None | N |
| V/T | 0.3502 | ambiguous | 0.2689 | benign | -2.293 | Highly Destabilizing | 0.009 | N | 0.4 | neutral | None | None | None | None | N |
| V/W | 0.9956 | likely_pathogenic | 0.9941 | pathogenic | -1.714 | Destabilizing | 0.992 | D | 0.823 | deleterious | None | None | None | None | N |
| V/Y | 0.9793 | likely_pathogenic | 0.9723 | pathogenic | -1.325 | Destabilizing | 0.972 | D | 0.775 | 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.