Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15032 | 45319;45320;45321 | chr2:178621730;178621729;178621728 | chr2:179486457;179486456;179486455 |
| N2AB | 13391 | 40396;40397;40398 | chr2:178621730;178621729;178621728 | chr2:179486457;179486456;179486455 |
| N2A | 12464 | 37615;37616;37617 | chr2:178621730;178621729;178621728 | chr2:179486457;179486456;179486455 |
| N2B | 5967 | 18124;18125;18126 | chr2:178621730;178621729;178621728 | chr2:179486457;179486456;179486455 |
| Novex-1 | 6092 | 18499;18500;18501 | chr2:178621730;178621729;178621728 | chr2:179486457;179486456;179486455 |
| Novex-2 | 6159 | 18700;18701;18702 | chr2:178621730;178621729;178621728 | chr2:179486457;179486456;179486455 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1358140088  |
None | 0.201 | N | 0.29 | 0.102 | 0.416328079214 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1358140088 |
None | 0.201 | N | 0.29 | 0.102 | 0.416328079214 | gnomAD-4.0.0 | 2.57058E-06 | None | None | None | None | N | None | 0 | 0 | None | 8.20345E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs768820093 |
-0.097 | 0.004 | N | 0.154 | 0.104 | 0.46017455471 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.73E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1385 | likely_benign | 0.1437 | benign | -0.822 | Destabilizing | 0.201 | N | 0.29 | neutral | N | 0.495732032 | None | None | N |
| V/C | 0.7451 | likely_pathogenic | 0.7596 | pathogenic | -0.791 | Destabilizing | 0.992 | D | 0.342 | neutral | None | None | None | None | N |
| V/D | 0.3124 | likely_benign | 0.3024 | benign | 0.287 | Stabilizing | 0.81 | D | 0.408 | neutral | N | 0.513657448 | None | None | N |
| V/E | 0.2135 | likely_benign | 0.2207 | benign | 0.286 | Stabilizing | 0.617 | D | 0.339 | neutral | None | None | None | None | N |
| V/F | 0.1547 | likely_benign | 0.1597 | benign | -0.553 | Destabilizing | 0.81 | D | 0.391 | neutral | N | 0.516057993 | None | None | N |
| V/G | 0.1785 | likely_benign | 0.1861 | benign | -1.099 | Destabilizing | 0.549 | D | 0.358 | neutral | D | 0.539766111 | None | None | N |
| V/H | 0.4202 | ambiguous | 0.447 | ambiguous | -0.518 | Destabilizing | 0.992 | D | 0.393 | neutral | None | None | None | None | N |
| V/I | 0.0786 | likely_benign | 0.0759 | benign | -0.188 | Destabilizing | 0.004 | N | 0.154 | neutral | N | 0.513909061 | None | None | N |
| V/K | 0.1947 | likely_benign | 0.1887 | benign | -0.469 | Destabilizing | 0.447 | N | 0.321 | neutral | None | None | None | None | N |
| V/L | 0.1582 | likely_benign | 0.1527 | benign | -0.188 | Destabilizing | 0.08 | N | 0.287 | neutral | N | 0.513334978 | None | None | N |
| V/M | 0.1344 | likely_benign | 0.1242 | benign | -0.367 | Destabilizing | 0.85 | D | 0.393 | neutral | None | None | None | None | N |
| V/N | 0.1967 | likely_benign | 0.2028 | benign | -0.349 | Destabilizing | 0.85 | D | 0.408 | neutral | None | None | None | None | N |
| V/P | 0.7111 | likely_pathogenic | 0.7082 | pathogenic | -0.362 | Destabilizing | 0.92 | D | 0.423 | neutral | None | None | None | None | N |
| V/Q | 0.2167 | likely_benign | 0.2297 | benign | -0.398 | Destabilizing | 0.85 | D | 0.419 | neutral | None | None | None | None | N |
| V/R | 0.1831 | likely_benign | 0.1856 | benign | -0.165 | Destabilizing | 0.005 | N | 0.291 | neutral | None | None | None | None | N |
| V/S | 0.15 | likely_benign | 0.1665 | benign | -0.982 | Destabilizing | 0.447 | N | 0.306 | neutral | None | None | None | None | N |
| V/T | 0.1335 | likely_benign | 0.1424 | benign | -0.848 | Destabilizing | 0.021 | N | 0.131 | neutral | None | None | None | None | N |
| V/W | 0.7882 | likely_pathogenic | 0.8091 | pathogenic | -0.681 | Destabilizing | 0.992 | D | 0.505 | neutral | None | None | None | None | N |
| V/Y | 0.4994 | ambiguous | 0.5267 | ambiguous | -0.359 | Destabilizing | 0.92 | D | 0.386 | 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.