Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25501 | 76726;76727;76728 | chr2:178569631;178569630;178569629 | chr2:179434358;179434357;179434356 |
| N2AB | 23860 | 71803;71804;71805 | chr2:178569631;178569630;178569629 | chr2:179434358;179434357;179434356 |
| N2A | 22933 | 69022;69023;69024 | chr2:178569631;178569630;178569629 | chr2:179434358;179434357;179434356 |
| N2B | 16436 | 49531;49532;49533 | chr2:178569631;178569630;178569629 | chr2:179434358;179434357;179434356 |
| Novex-1 | 16561 | 49906;49907;49908 | chr2:178569631;178569630;178569629 | chr2:179434358;179434357;179434356 |
| Novex-2 | 16628 | 50107;50108;50109 | chr2:178569631;178569630;178569629 | chr2:179434358;179434357;179434356 |
| 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/A | rs768730615  |
-3.159 | 0.067 | N | 0.199 | 0.136 | 0.223146558224 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.75E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs768730615 |
-3.159 | 0.067 | N | 0.199 | 0.136 | 0.223146558224 | gnomAD-4.0.0 | 1.3701E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53498E-05 | None | 0 | 0 | 9.00118E-07 | 0 | 0 |
| V/D | None | None | 0.974 | N | 0.769 | 0.367 | 0.54823119731 | gnomAD-4.0.0 | 6.85049E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00118E-07 | 0 | 0 |
| V/I | rs1266584718 |
-1.426 | 0.029 | N | 0.109 | 0.074 | 0.262175524916 | gnomAD-2.1.1 | 1.45E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.39E-05 | 1.42776E-04 |
| V/I | rs1266584718 |
-1.426 | 0.029 | N | 0.109 | 0.074 | 0.262175524916 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs1266584718 |
-1.426 | 0.029 | N | 0.109 | 0.074 | 0.262175524916 | gnomAD-4.0.0 | 4.96343E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.9376E-06 | 0 | 1.60349E-05 |
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 | 0.1692 | likely_benign | 0.189 | benign | -2.48 | Highly Destabilizing | 0.067 | N | 0.199 | neutral | N | 0.403470067 | None | None | N |
| V/C | 0.8187 | likely_pathogenic | 0.8476 | pathogenic | -2.209 | Highly Destabilizing | 0.998 | D | 0.622 | neutral | None | None | None | None | N |
| V/D | 0.9743 | likely_pathogenic | 0.9818 | pathogenic | -3.259 | Highly Destabilizing | 0.974 | D | 0.769 | deleterious | N | 0.459201288 | None | None | N |
| V/E | 0.938 | likely_pathogenic | 0.9533 | pathogenic | -3.044 | Highly Destabilizing | 0.981 | D | 0.659 | prob.neutral | None | None | None | None | N |
| V/F | 0.6971 | likely_pathogenic | 0.7493 | pathogenic | -1.385 | Destabilizing | 0.949 | D | 0.702 | prob.delet. | N | 0.455398945 | None | None | N |
| V/G | 0.5799 | likely_pathogenic | 0.6093 | pathogenic | -2.967 | Highly Destabilizing | 0.842 | D | 0.693 | prob.delet. | N | 0.458187329 | None | None | N |
| V/H | 0.9787 | likely_pathogenic | 0.9842 | pathogenic | -2.471 | Highly Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/I | 0.1021 | likely_benign | 0.1029 | benign | -1.105 | Destabilizing | 0.029 | N | 0.109 | neutral | N | 0.422730618 | None | None | N |
| V/K | 0.9455 | likely_pathogenic | 0.9598 | pathogenic | -1.96 | Destabilizing | 0.981 | D | 0.667 | prob.neutral | None | None | None | None | N |
| V/L | 0.316 | likely_benign | 0.3014 | benign | -1.105 | Destabilizing | 0.007 | N | 0.142 | neutral | N | 0.480277412 | None | None | N |
| V/M | 0.3238 | likely_benign | 0.348 | ambiguous | -1.429 | Destabilizing | 0.961 | D | 0.583 | neutral | None | None | None | None | N |
| V/N | 0.891 | likely_pathogenic | 0.9089 | pathogenic | -2.348 | Highly Destabilizing | 0.994 | D | 0.766 | deleterious | None | None | None | None | N |
| V/P | 0.402 | ambiguous | 0.4319 | ambiguous | -1.542 | Destabilizing | 0.981 | D | 0.738 | deleterious | None | None | None | None | N |
| V/Q | 0.9115 | likely_pathogenic | 0.9336 | pathogenic | -2.211 | Highly Destabilizing | 0.994 | D | 0.701 | prob.delet. | None | None | None | None | N |
| V/R | 0.9123 | likely_pathogenic | 0.9343 | pathogenic | -1.721 | Destabilizing | 0.981 | D | 0.776 | deleterious | None | None | None | None | N |
| V/S | 0.5639 | ambiguous | 0.6055 | pathogenic | -2.904 | Highly Destabilizing | 0.78 | D | 0.652 | prob.neutral | None | None | None | None | N |
| V/T | 0.3025 | likely_benign | 0.2985 | benign | -2.562 | Highly Destabilizing | 0.876 | D | 0.595 | neutral | None | None | None | None | N |
| V/W | 0.9889 | likely_pathogenic | 0.9916 | pathogenic | -1.812 | Destabilizing | 0.998 | D | 0.737 | deleterious | None | None | None | None | N |
| V/Y | 0.967 | likely_pathogenic | 0.9781 | pathogenic | -1.562 | Destabilizing | 0.994 | D | 0.729 | 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.