Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18895 | 56908;56909;56910 | chr2:178599027;178599026;178599025 | chr2:179463754;179463753;179463752 |
| N2AB | 17254 | 51985;51986;51987 | chr2:178599027;178599026;178599025 | chr2:179463754;179463753;179463752 |
| N2A | 16327 | 49204;49205;49206 | chr2:178599027;178599026;178599025 | chr2:179463754;179463753;179463752 |
| N2B | 9830 | 29713;29714;29715 | chr2:178599027;178599026;178599025 | chr2:179463754;179463753;179463752 |
| Novex-1 | 9955 | 30088;30089;30090 | chr2:178599027;178599026;178599025 | chr2:179463754;179463753;179463752 |
| Novex-2 | 10022 | 30289;30290;30291 | chr2:178599027;178599026;178599025 | chr2:179463754;179463753;179463752 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1289916968  |
-0.077 | 0.999 | N | 0.437 | 0.293 | 0.385417323374 | gnomAD-2.1.1 | 1.31E-05 | None | None | None | None | N | None | 6.71E-05 | 6.58E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs1289916968 |
-0.077 | 0.999 | N | 0.437 | 0.293 | 0.385417323374 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 1.31079E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs1289916968 |
-0.077 | 0.999 | N | 0.437 | 0.293 | 0.385417323374 | gnomAD-4.0.0 | 6.29312E-06 | None | None | None | None | N | None | 8.1226E-05 | 7.10152E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs1289916968 |
-0.565 | 0.826 | N | 0.344 | 0.098 | 0.257786959452 | gnomAD-2.1.1 | 4.36E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.49E-06 | 0 |
| S/G | rs1289916968 |
-0.565 | 0.826 | N | 0.344 | 0.098 | 0.257786959452 | gnomAD-4.0.0 | 1.39178E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.8194E-06 | 0 | 0 |
| S/I | rs2052561080 |
None | 0.996 | N | 0.492 | 0.347 | 0.496560916508 | gnomAD-4.0.0 | 1.65177E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.95688E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs375403059 |
0.044 | 0.99 | N | 0.43 | 0.239 | 0.357519025918 | gnomAD-2.1.1 | 4.33E-06 | None | None | None | None | N | None | 0 | 3.24E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs375403059 |
0.044 | 0.99 | N | 0.43 | 0.239 | 0.357519025918 | gnomAD-4.0.0 | 6.95199E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.09243E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0919 | likely_benign | 0.0871 | benign | -0.267 | Destabilizing | 0.863 | D | 0.389 | neutral | None | None | None | None | N |
| S/C | 0.1711 | likely_benign | 0.1691 | benign | -0.209 | Destabilizing | 0.999 | D | 0.437 | neutral | N | 0.503898925 | None | None | N |
| S/D | 0.5114 | ambiguous | 0.4433 | ambiguous | 0.136 | Stabilizing | 0.02 | N | 0.08 | neutral | None | None | None | None | N |
| S/E | 0.7012 | likely_pathogenic | 0.6068 | pathogenic | 0.026 | Stabilizing | 0.17 | N | 0.073 | neutral | None | None | None | None | N |
| S/F | 0.342 | ambiguous | 0.3308 | benign | -0.976 | Destabilizing | 0.997 | D | 0.481 | neutral | None | None | None | None | N |
| S/G | 0.1256 | likely_benign | 0.1217 | benign | -0.332 | Destabilizing | 0.826 | D | 0.344 | neutral | N | 0.480443276 | None | None | N |
| S/H | 0.5493 | ambiguous | 0.461 | ambiguous | -0.833 | Destabilizing | 0.997 | D | 0.427 | neutral | None | None | None | None | N |
| S/I | 0.424 | ambiguous | 0.3726 | ambiguous | -0.228 | Destabilizing | 0.996 | D | 0.492 | neutral | N | 0.506688514 | None | None | N |
| S/K | 0.9183 | likely_pathogenic | 0.8425 | pathogenic | -0.337 | Destabilizing | 0.939 | D | 0.327 | neutral | None | None | None | None | N |
| S/L | 0.1515 | likely_benign | 0.1394 | benign | -0.228 | Destabilizing | 0.969 | D | 0.445 | neutral | None | None | None | None | N |
| S/M | 0.2474 | likely_benign | 0.2199 | benign | 0.025 | Stabilizing | 0.999 | D | 0.41 | neutral | None | None | None | None | N |
| S/N | 0.2096 | likely_benign | 0.1739 | benign | -0.045 | Destabilizing | 0.92 | D | 0.383 | neutral | N | 0.428494303 | None | None | N |
| S/P | 0.9461 | likely_pathogenic | 0.927 | pathogenic | -0.215 | Destabilizing | 0.997 | D | 0.427 | neutral | None | None | None | None | N |
| S/Q | 0.6881 | likely_pathogenic | 0.5945 | pathogenic | -0.317 | Destabilizing | 0.939 | D | 0.365 | neutral | None | None | None | None | N |
| S/R | 0.8926 | likely_pathogenic | 0.8226 | pathogenic | -0.136 | Destabilizing | 0.99 | D | 0.43 | neutral | N | 0.490833628 | None | None | N |
| S/T | 0.1378 | likely_benign | 0.1231 | benign | -0.168 | Destabilizing | 0.959 | D | 0.377 | neutral | N | 0.483656939 | None | None | N |
| S/V | 0.3319 | likely_benign | 0.2923 | benign | -0.215 | Destabilizing | 0.969 | D | 0.463 | neutral | None | None | None | None | N |
| S/W | 0.5797 | likely_pathogenic | 0.5677 | pathogenic | -1.009 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | N |
| S/Y | 0.3242 | likely_benign | 0.2858 | benign | -0.708 | Destabilizing | 0.997 | D | 0.478 | neutral | 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.