Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30243 | 90952;90953;90954 | chr2:178552173;178552172;178552171 | chr2:179416900;179416899;179416898 |
| N2AB | 28602 | 86029;86030;86031 | chr2:178552173;178552172;178552171 | chr2:179416900;179416899;179416898 |
| N2A | 27675 | 83248;83249;83250 | chr2:178552173;178552172;178552171 | chr2:179416900;179416899;179416898 |
| N2B | 21178 | 63757;63758;63759 | chr2:178552173;178552172;178552171 | chr2:179416900;179416899;179416898 |
| Novex-1 | 21303 | 64132;64133;64134 | chr2:178552173;178552172;178552171 | chr2:179416900;179416899;179416898 |
| Novex-2 | 21370 | 64333;64334;64335 | chr2:178552173;178552172;178552171 | chr2:179416900;179416899;179416898 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs925184690  |
-1.546 | 0.982 | N | 0.493 | 0.318 | 0.453119318887 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 2.06612E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs925184690 |
-1.546 | 0.982 | N | 0.493 | 0.318 | 0.453119318887 | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | I | None | 2.17035E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/F | rs925184690 |
-1.546 | 0.982 | N | 0.493 | 0.318 | 0.453119318887 | gnomAD-4.0.0 | 1.05345E-05 | None | None | None | None | I | None | 2.2686E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs753176908 |
-1.158 | 0.991 | N | 0.523 | 0.219 | 0.442466506703 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/M | rs753176908 |
-1.158 | 0.991 | N | 0.523 | 0.219 | 0.442466506703 | gnomAD-4.0.0 | 1.59123E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02352E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4328 | ambiguous | 0.4346 | ambiguous | -2.111 | Highly Destabilizing | 0.91 | D | 0.473 | neutral | None | None | None | None | I |
| I/C | 0.6179 | likely_pathogenic | 0.6276 | pathogenic | -1.608 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | I |
| I/D | 0.8776 | likely_pathogenic | 0.8593 | pathogenic | -1.861 | Destabilizing | 0.998 | D | 0.748 | deleterious | None | None | None | None | I |
| I/E | 0.7851 | likely_pathogenic | 0.7668 | pathogenic | -1.764 | Destabilizing | 0.993 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/F | 0.2171 | likely_benign | 0.2122 | benign | -1.34 | Destabilizing | 0.982 | D | 0.493 | neutral | N | 0.500375831 | None | None | I |
| I/G | 0.7472 | likely_pathogenic | 0.7465 | pathogenic | -2.531 | Highly Destabilizing | 0.993 | D | 0.715 | prob.delet. | None | None | None | None | I |
| I/H | 0.5916 | likely_pathogenic | 0.5402 | ambiguous | -1.751 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | I |
| I/K | 0.6403 | likely_pathogenic | 0.5778 | pathogenic | -1.453 | Destabilizing | 0.993 | D | 0.732 | prob.delet. | None | None | None | None | I |
| I/L | 0.1315 | likely_benign | 0.1242 | benign | -0.969 | Destabilizing | 0.58 | D | 0.388 | neutral | N | 0.459662572 | None | None | I |
| I/M | 0.1218 | likely_benign | 0.1136 | benign | -0.974 | Destabilizing | 0.991 | D | 0.523 | neutral | N | 0.448216214 | None | None | I |
| I/N | 0.3638 | ambiguous | 0.32 | benign | -1.471 | Destabilizing | 0.997 | D | 0.759 | deleterious | N | 0.452717957 | None | None | I |
| I/P | 0.9674 | likely_pathogenic | 0.9565 | pathogenic | -1.323 | Destabilizing | 0.998 | D | 0.755 | deleterious | None | None | None | None | I |
| I/Q | 0.5906 | likely_pathogenic | 0.5614 | ambiguous | -1.554 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | I |
| I/R | 0.5575 | ambiguous | 0.4852 | ambiguous | -0.973 | Destabilizing | 0.993 | D | 0.758 | deleterious | None | None | None | None | I |
| I/S | 0.3257 | likely_benign | 0.3097 | benign | -2.189 | Highly Destabilizing | 0.991 | D | 0.635 | neutral | N | 0.447482708 | None | None | I |
| I/T | 0.191 | likely_benign | 0.1907 | benign | -1.965 | Destabilizing | 0.939 | D | 0.519 | neutral | N | 0.3426434 | None | None | I |
| I/V | 0.0748 | likely_benign | 0.0775 | benign | -1.323 | Destabilizing | 0.02 | N | 0.245 | neutral | N | 0.391090708 | None | None | I |
| I/W | 0.8426 | likely_pathogenic | 0.8225 | pathogenic | -1.5 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | I |
| I/Y | 0.584 | likely_pathogenic | 0.5105 | ambiguous | -1.25 | Destabilizing | 0.993 | D | 0.616 | 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.