Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17894 | 53905;53906;53907 | chr2:178605615;178605614;178605613 | chr2:179470342;179470341;179470340 |
| N2AB | 16253 | 48982;48983;48984 | chr2:178605615;178605614;178605613 | chr2:179470342;179470341;179470340 |
| N2A | 15326 | 46201;46202;46203 | chr2:178605615;178605614;178605613 | chr2:179470342;179470341;179470340 |
| N2B | 8829 | 26710;26711;26712 | chr2:178605615;178605614;178605613 | chr2:179470342;179470341;179470340 |
| Novex-1 | 8954 | 27085;27086;27087 | chr2:178605615;178605614;178605613 | chr2:179470342;179470341;179470340 |
| Novex-2 | 9021 | 27286;27287;27288 | chr2:178605615;178605614;178605613 | chr2:179470342;179470341;179470340 |
| 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/T | None | None | 0.989 | N | 0.813 | 0.58 | 0.693353280975 | gnomAD-4.0.0 | 1.59557E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78118E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1200778787  |
-1.587 | 0.333 | N | 0.263 | 0.083 | 0.391000631824 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/V | rs1200778787 |
-1.587 | 0.333 | N | 0.263 | 0.083 | 0.391000631824 | gnomAD-4.0.0 | 1.59461E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86533E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9589 | likely_pathogenic | 0.919 | pathogenic | -2.179 | Highly Destabilizing | 0.992 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.9479 | likely_pathogenic | 0.9246 | pathogenic | -1.308 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| I/D | 0.9939 | likely_pathogenic | 0.9886 | pathogenic | -1.867 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/E | 0.9878 | likely_pathogenic | 0.9768 | pathogenic | -1.797 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/F | 0.7591 | likely_pathogenic | 0.6546 | pathogenic | -1.423 | Destabilizing | 0.998 | D | 0.75 | deleterious | N | 0.519105546 | None | None | N |
| I/G | 0.9915 | likely_pathogenic | 0.9813 | pathogenic | -2.589 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| I/H | 0.9785 | likely_pathogenic | 0.9588 | pathogenic | -1.825 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| I/K | 0.9772 | likely_pathogenic | 0.9555 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/L | 0.2202 | likely_benign | 0.1786 | benign | -1.072 | Destabilizing | 0.889 | D | 0.481 | neutral | N | 0.51881245 | None | None | N |
| I/M | 0.4349 | ambiguous | 0.3448 | ambiguous | -0.805 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | N | 0.521640441 | None | None | N |
| I/N | 0.8266 | likely_pathogenic | 0.7678 | pathogenic | -1.478 | Destabilizing | 0.999 | D | 0.833 | deleterious | N | 0.51113351 | None | None | N |
| I/P | 0.9229 | likely_pathogenic | 0.8862 | pathogenic | -1.413 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| I/Q | 0.975 | likely_pathogenic | 0.9509 | pathogenic | -1.591 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| I/R | 0.9669 | likely_pathogenic | 0.9367 | pathogenic | -1.022 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| I/S | 0.9385 | likely_pathogenic | 0.8947 | pathogenic | -2.137 | Highly Destabilizing | 0.998 | D | 0.795 | deleterious | D | 0.533250236 | None | None | N |
| I/T | 0.9046 | likely_pathogenic | 0.8449 | pathogenic | -1.944 | Destabilizing | 0.989 | D | 0.813 | deleterious | N | 0.499016736 | None | None | N |
| I/V | 0.1284 | likely_benign | 0.1081 | benign | -1.413 | Destabilizing | 0.333 | N | 0.263 | neutral | N | 0.45653184 | None | None | N |
| I/W | 0.9902 | likely_pathogenic | 0.9833 | pathogenic | -1.583 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| I/Y | 0.9568 | likely_pathogenic | 0.9288 | pathogenic | -1.378 | Destabilizing | 1.0 | D | 0.804 | deleterious | 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.