Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4636 | 14131;14132;14133 | chr2:178739327;178739326;178739325 | chr2:179604054;179604053;179604052 |
| N2AB | 4319 | 13180;13181;13182 | chr2:178739327;178739326;178739325 | chr2:179604054;179604053;179604052 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4273 | 13042;13043;13044 | chr2:178739327;178739326;178739325 | chr2:179604054;179604053;179604052 |
| Novex-1 | 4398 | 13417;13418;13419 | chr2:178739327;178739326;178739325 | chr2:179604054;179604053;179604052 |
| Novex-2 | 4465 | 13618;13619;13620 | chr2:178739327;178739326;178739325 | chr2:179604054;179604053;179604052 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs773324490  |
-0.767 | 0.324 | N | 0.529 | 0.08 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 3.08801E-04 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs773324490 |
-0.767 | 0.324 | N | 0.529 | 0.08 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs773324490 |
-0.767 | 0.324 | N | 0.529 | 0.08 | None | gnomAD-4.0.0 | 7.68673E-06 | None | None | None | None | N | None | 1.69039E-05 | 0 | None | 0 | 7.28403E-05 | None | 0 | 2.24215E-04 | 2.39295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.276 | likely_benign | 0.3128 | benign | -0.989 | Destabilizing | 0.388 | N | 0.557 | neutral | None | None | None | None | N |
| N/C | 0.2668 | likely_benign | 0.2645 | benign | -0.073 | Destabilizing | 0.981 | D | 0.627 | neutral | None | None | None | None | N |
| N/D | 0.2344 | likely_benign | 0.2575 | benign | -0.63 | Destabilizing | 0.324 | N | 0.515 | neutral | N | 0.508215335 | None | None | N |
| N/E | 0.3943 | ambiguous | 0.4501 | ambiguous | -0.459 | Destabilizing | 0.241 | N | 0.499 | neutral | None | None | None | None | N |
| N/F | 0.4554 | ambiguous | 0.4787 | ambiguous | -0.478 | Destabilizing | 0.527 | D | 0.615 | neutral | None | None | None | None | N |
| N/G | 0.3855 | ambiguous | 0.4328 | ambiguous | -1.38 | Destabilizing | 0.388 | N | 0.511 | neutral | None | None | None | None | N |
| N/H | 0.0893 | likely_benign | 0.094 | benign | -0.851 | Destabilizing | 0.003 | N | 0.362 | neutral | N | 0.507930713 | None | None | N |
| N/I | 0.1917 | likely_benign | 0.2183 | benign | 0.044 | Stabilizing | 0.015 | N | 0.514 | neutral | N | 0.500697758 | None | None | N |
| N/K | 0.1839 | likely_benign | 0.228 | benign | -0.294 | Destabilizing | 0.006 | N | 0.353 | neutral | N | 0.484685051 | None | None | N |
| N/L | 0.2342 | likely_benign | 0.2787 | benign | 0.044 | Stabilizing | 0.241 | N | 0.555 | neutral | None | None | None | None | N |
| N/M | 0.3284 | likely_benign | 0.3612 | ambiguous | 0.31 | Stabilizing | 0.944 | D | 0.584 | neutral | None | None | None | None | N |
| N/P | 0.9388 | likely_pathogenic | 0.9576 | pathogenic | -0.272 | Destabilizing | 0.818 | D | 0.605 | neutral | None | None | None | None | N |
| N/Q | 0.2616 | likely_benign | 0.3021 | benign | -0.721 | Destabilizing | 0.69 | D | 0.532 | neutral | None | None | None | None | N |
| N/R | 0.1899 | likely_benign | 0.2294 | benign | -0.414 | Destabilizing | 0.241 | N | 0.517 | neutral | None | None | None | None | N |
| N/S | 0.0984 | likely_benign | 0.1043 | benign | -1.069 | Destabilizing | 0.324 | N | 0.529 | neutral | N | 0.488990399 | None | None | N |
| N/T | 0.1421 | likely_benign | 0.1595 | benign | -0.697 | Destabilizing | 0.492 | N | 0.505 | neutral | N | 0.470282287 | None | None | N |
| N/V | 0.2397 | likely_benign | 0.2711 | benign | -0.272 | Destabilizing | 0.241 | N | 0.568 | neutral | None | None | None | None | N |
| N/W | 0.7178 | likely_pathogenic | 0.7416 | pathogenic | -0.257 | Destabilizing | 0.944 | D | 0.631 | neutral | None | None | None | None | N |
| N/Y | 0.1457 | likely_benign | 0.1507 | benign | -0.029 | Destabilizing | 0.003 | N | 0.467 | neutral | N | 0.508647459 | 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.