Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31917 | 95974;95975;95976 | chr2:178544480;178544479;178544478 | chr2:179409207;179409206;179409205 |
| N2AB | 30276 | 91051;91052;91053 | chr2:178544480;178544479;178544478 | chr2:179409207;179409206;179409205 |
| N2A | 29349 | 88270;88271;88272 | chr2:178544480;178544479;178544478 | chr2:179409207;179409206;179409205 |
| N2B | 22852 | 68779;68780;68781 | chr2:178544480;178544479;178544478 | chr2:179409207;179409206;179409205 |
| Novex-1 | 22977 | 69154;69155;69156 | chr2:178544480;178544479;178544478 | chr2:179409207;179409206;179409205 |
| Novex-2 | 23044 | 69355;69356;69357 | chr2:178544480;178544479;178544478 | chr2:179409207;179409206;179409205 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs762845985  |
0.124 | 1.0 | N | 0.775 | 0.314 | 0.256793551483 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| R/S | rs762845985 |
0.124 | 1.0 | N | 0.775 | 0.314 | 0.256793551483 | gnomAD-4.0.0 | 4.81141E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.3288E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4845 | ambiguous | 0.4986 | ambiguous | -0.811 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| R/C | 0.1881 | likely_benign | 0.2011 | benign | -0.821 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/D | 0.7596 | likely_pathogenic | 0.7831 | pathogenic | -0.007 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| R/E | 0.4458 | ambiguous | 0.4611 | ambiguous | 0.145 | Stabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/F | 0.5077 | ambiguous | 0.5537 | ambiguous | -0.5 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/G | 0.4341 | ambiguous | 0.4483 | ambiguous | -1.145 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.473636964 | None | None | N |
| R/H | 0.1038 | likely_benign | 0.1134 | benign | -1.383 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/I | 0.2964 | likely_benign | 0.308 | benign | 0.097 | Stabilizing | 1.0 | D | 0.781 | deleterious | N | 0.51074754 | None | None | N |
| R/K | 0.1004 | likely_benign | 0.1098 | benign | -0.774 | Destabilizing | 0.997 | D | 0.537 | neutral | N | 0.421682974 | None | None | N |
| R/L | 0.2987 | likely_benign | 0.3054 | benign | 0.097 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/M | 0.3367 | likely_benign | 0.3442 | ambiguous | -0.378 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| R/N | 0.625 | likely_pathogenic | 0.6673 | pathogenic | -0.402 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| R/P | 0.9452 | likely_pathogenic | 0.9358 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/Q | 0.1277 | likely_benign | 0.1294 | benign | -0.463 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| R/S | 0.5633 | ambiguous | 0.5895 | pathogenic | -1.162 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.475842745 | None | None | N |
| R/T | 0.3157 | likely_benign | 0.332 | benign | -0.815 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.473765232 | None | None | N |
| R/V | 0.3416 | ambiguous | 0.3492 | ambiguous | -0.185 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/W | 0.2116 | likely_benign | 0.2163 | benign | -0.149 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/Y | 0.3717 | ambiguous | 0.4055 | ambiguous | 0.122 | Stabilizing | 1.0 | D | 0.792 | 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.