Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22607 | 68044;68045;68046 | chr2:178579211;178579210;178579209 | chr2:179443938;179443937;179443936 |
| N2AB | 20966 | 63121;63122;63123 | chr2:178579211;178579210;178579209 | chr2:179443938;179443937;179443936 |
| N2A | 20039 | 60340;60341;60342 | chr2:178579211;178579210;178579209 | chr2:179443938;179443937;179443936 |
| N2B | 13542 | 40849;40850;40851 | chr2:178579211;178579210;178579209 | chr2:179443938;179443937;179443936 |
| Novex-1 | 13667 | 41224;41225;41226 | chr2:178579211;178579210;178579209 | chr2:179443938;179443937;179443936 |
| Novex-2 | 13734 | 41425;41426;41427 | chr2:178579211;178579210;178579209 | chr2:179443938;179443937;179443936 |
| 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/I | rs771603862  |
0.046 | 0.1 | N | 0.413 | 0.302 | 0.474010150167 | gnomAD-2.1.1 | 4.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.94137E-04 | None | 0 | 2.67E-05 | 0 |
| T/I | rs771603862 |
0.046 | 0.1 | N | 0.413 | 0.302 | 0.474010150167 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 6.22407E-04 | 0 |
| T/I | rs771603862 |
0.046 | 0.1 | N | 0.413 | 0.302 | 0.474010150167 | gnomAD-4.0.0 | 2.41736E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.3254E-06 | 2.85513E-04 | 3.20318E-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 | 0.1047 | likely_benign | 0.1146 | benign | -1.385 | Destabilizing | 0.863 | D | 0.591 | neutral | N | 0.497777239 | None | None | N |
| T/C | 0.4666 | ambiguous | 0.483 | ambiguous | -1.255 | Destabilizing | 0.999 | D | 0.62 | neutral | None | None | None | None | N |
| T/D | 0.7515 | likely_pathogenic | 0.7438 | pathogenic | -2.203 | Highly Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | N |
| T/E | 0.5665 | likely_pathogenic | 0.5474 | ambiguous | -1.96 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| T/F | 0.414 | ambiguous | 0.3939 | ambiguous | -0.967 | Destabilizing | 0.986 | D | 0.674 | neutral | None | None | None | None | N |
| T/G | 0.4393 | ambiguous | 0.4827 | ambiguous | -1.807 | Destabilizing | 0.998 | D | 0.659 | neutral | None | None | None | None | N |
| T/H | 0.4569 | ambiguous | 0.4472 | ambiguous | -1.874 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| T/I | 0.2069 | likely_benign | 0.1761 | benign | -0.262 | Destabilizing | 0.1 | N | 0.413 | neutral | N | 0.513092491 | None | None | N |
| T/K | 0.586 | likely_pathogenic | 0.5361 | ambiguous | -0.775 | Destabilizing | 0.993 | D | 0.635 | neutral | None | None | None | None | N |
| T/L | 0.1601 | likely_benign | 0.1466 | benign | -0.262 | Destabilizing | 0.807 | D | 0.574 | neutral | None | None | None | None | N |
| T/M | 0.1107 | likely_benign | 0.1094 | benign | -0.449 | Destabilizing | 0.986 | D | 0.634 | neutral | None | None | None | None | N |
| T/N | 0.2612 | likely_benign | 0.261 | benign | -1.656 | Destabilizing | 0.997 | D | 0.696 | prob.neutral | D | 0.525770999 | None | None | N |
| T/P | 0.8892 | likely_pathogenic | 0.8629 | pathogenic | -0.608 | Destabilizing | 0.997 | D | 0.658 | neutral | D | 0.525796222 | None | None | N |
| T/Q | 0.4196 | ambiguous | 0.4122 | ambiguous | -1.328 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| T/R | 0.5179 | ambiguous | 0.463 | ambiguous | -1.065 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| T/S | 0.1425 | likely_benign | 0.1578 | benign | -1.794 | Destabilizing | 0.969 | D | 0.603 | neutral | N | 0.482940155 | None | None | N |
| T/V | 0.141 | likely_benign | 0.1282 | benign | -0.608 | Destabilizing | 0.214 | N | 0.433 | neutral | None | None | None | None | N |
| T/W | 0.7917 | likely_pathogenic | 0.7723 | pathogenic | -1.217 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4537 | ambiguous | 0.4366 | ambiguous | -0.812 | Destabilizing | 0.998 | D | 0.676 | prob.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.