Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8997 | 27214;27215;27216 | chr2:178713145;178713144;178713143 | chr2:179577872;179577871;179577870 |
| N2AB | 8680 | 26263;26264;26265 | chr2:178713145;178713144;178713143 | chr2:179577872;179577871;179577870 |
| N2A | 7753 | 23482;23483;23484 | chr2:178713145;178713144;178713143 | chr2:179577872;179577871;179577870 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/A | rs953177976  |
None | 0.454 | N | 0.407 | 0.218 | 0.228597637076 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs953177976 |
None | 0.454 | N | 0.407 | 0.218 | 0.228597637076 | gnomAD-4.0.0 | 1.31406E-05 | None | None | None | None | N | None | 4.82556E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1259415133 |
0.22 | 0.669 | N | 0.55 | 0.19 | 0.419461527279 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| T/I | rs1259415133 |
0.22 | 0.669 | N | 0.55 | 0.19 | 0.419461527279 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs1259415133 |
0.22 | 0.669 | N | 0.55 | 0.19 | 0.419461527279 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 0 | 0 |
| T/R | rs1259415133 |
-0.407 | 0.669 | N | 0.549 | 0.2 | 0.5253096542 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| T/R | rs1259415133 |
-0.407 | 0.669 | N | 0.549 | 0.2 | 0.5253096542 | gnomAD-4.0.0 | 3.18277E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.76563E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.089 | likely_benign | 0.0957 | benign | -1.165 | Destabilizing | 0.454 | N | 0.407 | neutral | N | 0.478764028 | None | None | N |
| T/C | 0.3657 | ambiguous | 0.4202 | ambiguous | -0.47 | Destabilizing | 0.998 | D | 0.603 | neutral | None | None | None | None | N |
| T/D | 0.5186 | ambiguous | 0.5479 | ambiguous | -1.203 | Destabilizing | 0.842 | D | 0.537 | neutral | None | None | None | None | N |
| T/E | 0.3361 | likely_benign | 0.3611 | ambiguous | -0.954 | Destabilizing | 0.842 | D | 0.553 | neutral | None | None | None | None | N |
| T/F | 0.2008 | likely_benign | 0.2288 | benign | -0.865 | Destabilizing | 0.949 | D | 0.579 | neutral | None | None | None | None | N |
| T/G | 0.3083 | likely_benign | 0.3202 | benign | -1.593 | Destabilizing | 0.728 | D | 0.565 | neutral | None | None | None | None | N |
| T/H | 0.1728 | likely_benign | 0.1764 | benign | -1.518 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| T/I | 0.1207 | likely_benign | 0.1464 | benign | -0.014 | Destabilizing | 0.669 | D | 0.55 | neutral | N | 0.467394495 | None | None | N |
| T/K | 0.1254 | likely_benign | 0.1328 | benign | 0.218 | Stabilizing | 0.051 | N | 0.401 | neutral | N | 0.459899304 | None | None | N |
| T/L | 0.0977 | likely_benign | 0.105 | benign | -0.014 | Destabilizing | 0.016 | N | 0.368 | neutral | None | None | None | None | N |
| T/M | 0.0915 | likely_benign | 0.1035 | benign | -0.144 | Destabilizing | 0.325 | N | 0.498 | neutral | None | None | None | None | N |
| T/N | 0.1641 | likely_benign | 0.1828 | benign | -0.581 | Destabilizing | 0.842 | D | 0.534 | neutral | None | None | None | None | N |
| T/P | 0.7723 | likely_pathogenic | 0.8132 | pathogenic | -0.37 | Destabilizing | 0.966 | D | 0.581 | neutral | D | 0.524633776 | None | None | N |
| T/Q | 0.1838 | likely_benign | 0.1945 | benign | -0.292 | Destabilizing | 0.949 | D | 0.583 | neutral | None | None | None | None | N |
| T/R | 0.087 | likely_benign | 0.0913 | benign | -0.178 | Destabilizing | 0.669 | D | 0.549 | neutral | N | 0.459468004 | None | None | N |
| T/S | 0.1081 | likely_benign | 0.1077 | benign | -0.887 | Destabilizing | 0.022 | N | 0.241 | neutral | N | 0.516278285 | None | None | N |
| T/V | 0.112 | likely_benign | 0.1239 | benign | -0.37 | Destabilizing | 0.525 | D | 0.498 | neutral | None | None | None | None | N |
| T/W | 0.5419 | ambiguous | 0.5761 | pathogenic | -0.981 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| T/Y | 0.2306 | likely_benign | 0.256 | benign | -0.568 | Destabilizing | 0.974 | D | 0.573 | 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.