Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15993 | 48202;48203;48204 | chr2:178616912;178616911;178616910 | chr2:179481639;179481638;179481637 |
| N2AB | 14352 | 43279;43280;43281 | chr2:178616912;178616911;178616910 | chr2:179481639;179481638;179481637 |
| N2A | 13425 | 40498;40499;40500 | chr2:178616912;178616911;178616910 | chr2:179481639;179481638;179481637 |
| N2B | 6928 | 21007;21008;21009 | chr2:178616912;178616911;178616910 | chr2:179481639;179481638;179481637 |
| Novex-1 | 7053 | 21382;21383;21384 | chr2:178616912;178616911;178616910 | chr2:179481639;179481638;179481637 |
| Novex-2 | 7120 | 21583;21584;21585 | chr2:178616912;178616911;178616910 | chr2:179481639;179481638;179481637 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1483141685  |
-0.439 | 0.012 | D | 0.372 | 0.121 | 0.193865811164 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs1483141685 |
-0.439 | 0.012 | D | 0.372 | 0.121 | 0.193865811164 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs1483141685 |
-0.439 | 0.012 | D | 0.372 | 0.121 | 0.193865811164 | gnomAD-4.0.0 | 3.72059E-06 | None | None | None | None | I | None | 0 | 3.33879E-05 | None | 0 | 0 | None | 0 | 0 | 1.69609E-06 | 2.19621E-05 | 0 |
| T/N | rs727503622 |
-0.226 | 0.029 | N | 0.511 | 0.147 | 0.28492961333 | gnomAD-2.1.1 | 4.85E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.80143E-04 | None | 3.27E-05 | None | 0 | 4.48E-05 | 1.66389E-04 |
| T/N | rs727503622 |
-0.226 | 0.029 | N | 0.511 | 0.147 | 0.28492961333 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.8956E-04 | None | 0 | 0 | 4.42E-05 | 2.07383E-04 | 0 |
| T/N | rs727503622 |
-0.226 | 0.029 | N | 0.511 | 0.147 | 0.28492961333 | gnomAD-4.0.0 | 5.95271E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.61009E-03 | None | 0 | 0 | 1.18729E-05 | 6.5895E-05 | 6.40841E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0894 | likely_benign | 0.0793 | benign | -0.606 | Destabilizing | 0.012 | N | 0.372 | neutral | D | 0.545047079 | None | None | I |
| T/C | 0.4555 | ambiguous | 0.3974 | ambiguous | -0.349 | Destabilizing | 0.864 | D | 0.575 | neutral | None | None | None | None | I |
| T/D | 0.3353 | likely_benign | 0.3043 | benign | -0.016 | Destabilizing | 0.072 | N | 0.583 | neutral | None | None | None | None | I |
| T/E | 0.199 | likely_benign | 0.1836 | benign | -0.056 | Destabilizing | 0.038 | N | 0.527 | neutral | None | None | None | None | I |
| T/F | 0.257 | likely_benign | 0.242 | benign | -0.826 | Destabilizing | 0.214 | N | 0.595 | neutral | None | None | None | None | I |
| T/G | 0.2909 | likely_benign | 0.2678 | benign | -0.814 | Destabilizing | 0.072 | N | 0.542 | neutral | None | None | None | None | I |
| T/H | 0.2426 | likely_benign | 0.2214 | benign | -1.118 | Destabilizing | 0.001 | N | 0.373 | neutral | None | None | None | None | I |
| T/I | 0.1308 | likely_benign | 0.1201 | benign | -0.16 | Destabilizing | 0.001 | N | 0.291 | neutral | D | 0.547492963 | None | None | I |
| T/K | 0.1135 | likely_benign | 0.1092 | benign | -0.629 | Destabilizing | None | N | 0.267 | neutral | None | None | None | None | I |
| T/L | 0.0982 | likely_benign | 0.096 | benign | -0.16 | Destabilizing | 0.016 | N | 0.392 | neutral | None | None | None | None | I |
| T/M | 0.1171 | likely_benign | 0.1007 | benign | 0.089 | Stabilizing | 0.356 | N | 0.61 | neutral | None | None | None | None | I |
| T/N | 0.129 | likely_benign | 0.12 | benign | -0.413 | Destabilizing | 0.029 | N | 0.511 | neutral | N | 0.512476703 | None | None | I |
| T/P | 0.354 | ambiguous | 0.3413 | ambiguous | -0.277 | Destabilizing | 0.295 | N | 0.636 | neutral | D | 0.615111744 | None | None | I |
| T/Q | 0.1889 | likely_benign | 0.1626 | benign | -0.627 | Destabilizing | 0.12 | N | 0.645 | neutral | None | None | None | None | I |
| T/R | 0.121 | likely_benign | 0.1163 | benign | -0.357 | Destabilizing | 0.038 | N | 0.584 | neutral | None | None | None | None | I |
| T/S | 0.1131 | likely_benign | 0.1043 | benign | -0.67 | Destabilizing | 0.012 | N | 0.448 | neutral | N | 0.520030278 | None | None | I |
| T/V | 0.1079 | likely_benign | 0.1015 | benign | -0.277 | Destabilizing | None | N | 0.194 | neutral | None | None | None | None | I |
| T/W | 0.6475 | likely_pathogenic | 0.5961 | pathogenic | -0.773 | Destabilizing | 0.864 | D | 0.586 | neutral | None | None | None | None | I |
| T/Y | 0.3057 | likely_benign | 0.2698 | benign | -0.539 | Destabilizing | 0.12 | N | 0.611 | 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.