Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19490 | 58693;58694;58695 | chr2:178593832;178593831;178593830 | chr2:179458559;179458558;179458557 |
| N2AB | 17849 | 53770;53771;53772 | chr2:178593832;178593831;178593830 | chr2:179458559;179458558;179458557 |
| N2A | 16922 | 50989;50990;50991 | chr2:178593832;178593831;178593830 | chr2:179458559;179458558;179458557 |
| N2B | 10425 | 31498;31499;31500 | chr2:178593832;178593831;178593830 | chr2:179458559;179458558;179458557 |
| Novex-1 | 10550 | 31873;31874;31875 | chr2:178593832;178593831;178593830 | chr2:179458559;179458558;179458557 |
| Novex-2 | 10617 | 32074;32075;32076 | chr2:178593832;178593831;178593830 | chr2:179458559;179458558;179458557 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs374118468  |
-0.225 | 0.996 | N | 0.402 | 0.143 | 0.257786959452 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| D/E | rs374118468 |
-0.225 | 0.996 | N | 0.402 | 0.143 | 0.257786959452 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 3.87747E-04 | None | 0 | 0 | 0 | 4.13736E-04 | 4.78469E-04 |
| D/E | rs374118468 |
-0.225 | 0.996 | N | 0.402 | 0.143 | 0.257786959452 | gnomAD-4.0.0 | 4.10718E-06 | None | None | None | None | N | None | 0 | 2.24034E-05 | None | 0 | 0 | None | 0 | 0 | 4.49811E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1752 | likely_benign | 0.1962 | benign | -0.503 | Destabilizing | 0.999 | D | 0.647 | neutral | N | 0.494737937 | None | None | N |
| D/C | 0.5621 | ambiguous | 0.5867 | pathogenic | 0.002 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| D/E | 0.1179 | likely_benign | 0.1309 | benign | -0.346 | Destabilizing | 0.996 | D | 0.402 | neutral | N | 0.458950496 | None | None | N |
| D/F | 0.5993 | likely_pathogenic | 0.6406 | pathogenic | -0.401 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| D/G | 0.2101 | likely_benign | 0.2348 | benign | -0.722 | Destabilizing | 0.996 | D | 0.565 | neutral | N | 0.511054184 | None | None | N |
| D/H | 0.2416 | likely_benign | 0.2633 | benign | -0.371 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.501087907 | None | None | N |
| D/I | 0.302 | likely_benign | 0.3228 | benign | 0.036 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| D/K | 0.3182 | likely_benign | 0.3397 | benign | 0.27 | Stabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| D/L | 0.3076 | likely_benign | 0.3304 | benign | 0.036 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/M | 0.5363 | ambiguous | 0.5612 | ambiguous | 0.3 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| D/N | 0.1085 | likely_benign | 0.1117 | benign | -0.106 | Destabilizing | 0.767 | D | 0.211 | neutral | N | 0.466671523 | None | None | N |
| D/P | 0.9001 | likely_pathogenic | 0.9066 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/Q | 0.2699 | likely_benign | 0.2987 | benign | -0.07 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | N |
| D/R | 0.3675 | ambiguous | 0.3974 | ambiguous | 0.382 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| D/S | 0.1155 | likely_benign | 0.1231 | benign | -0.224 | Destabilizing | 0.997 | D | 0.532 | neutral | None | None | None | None | N |
| D/T | 0.1827 | likely_benign | 0.1939 | benign | -0.047 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| D/V | 0.1788 | likely_benign | 0.1972 | benign | -0.122 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.476786895 | None | None | N |
| D/W | 0.862 | likely_pathogenic | 0.8805 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| D/Y | 0.2507 | likely_benign | 0.2853 | benign | -0.151 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.471052843 | 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.