Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16137 | 48634;48635;48636 | chr2:178615692;178615691;178615690 | chr2:179480419;179480418;179480417 |
| N2AB | 14496 | 43711;43712;43713 | chr2:178615692;178615691;178615690 | chr2:179480419;179480418;179480417 |
| N2A | 13569 | 40930;40931;40932 | chr2:178615692;178615691;178615690 | chr2:179480419;179480418;179480417 |
| N2B | 7072 | 21439;21440;21441 | chr2:178615692;178615691;178615690 | chr2:179480419;179480418;179480417 |
| Novex-1 | 7197 | 21814;21815;21816 | chr2:178615692;178615691;178615690 | chr2:179480419;179480418;179480417 |
| Novex-2 | 7264 | 22015;22016;22017 | chr2:178615692;178615691;178615690 | chr2:179480419;179480418;179480417 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs982994931  |
-0.135 | 0.998 | N | 0.811 | 0.419 | 0.461759001683 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs982994931 |
-0.135 | 0.998 | N | 0.811 | 0.419 | 0.461759001683 | gnomAD-4.0.0 | 1.59387E-06 | None | None | None | None | N | None | 0 | 2.28781E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs879009898 |
None | 0.978 | N | 0.697 | 0.337 | 0.273938319068 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs879009898 |
None | 0.978 | N | 0.697 | 0.337 | 0.273938319068 | gnomAD-4.0.0 | 1.17846E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61158E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0843 | likely_benign | 0.088 | benign | -1.274 | Destabilizing | 0.543 | D | 0.424 | neutral | N | 0.46706209 | None | None | N |
| P/C | 0.5247 | ambiguous | 0.5682 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| P/D | 0.5137 | ambiguous | 0.5072 | ambiguous | -1.254 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | None | None | None | None | N |
| P/E | 0.3108 | likely_benign | 0.3171 | benign | -1.334 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/F | 0.4342 | ambiguous | 0.4574 | ambiguous | -1.259 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| P/G | 0.444 | ambiguous | 0.4272 | ambiguous | -1.502 | Destabilizing | 0.992 | D | 0.73 | prob.delet. | None | None | None | None | N |
| P/H | 0.3028 | likely_benign | 0.3242 | benign | -0.984 | Destabilizing | 0.595 | D | 0.562 | neutral | N | 0.516641236 | None | None | N |
| P/I | 0.2108 | likely_benign | 0.2291 | benign | -0.776 | Destabilizing | 0.999 | D | 0.816 | deleterious | None | None | None | None | N |
| P/K | 0.4376 | ambiguous | 0.449 | ambiguous | -1.0 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| P/L | 0.1113 | likely_benign | 0.1254 | benign | -0.776 | Destabilizing | 0.997 | D | 0.769 | deleterious | N | 0.473951252 | None | None | N |
| P/M | 0.2711 | likely_benign | 0.2864 | benign | -0.45 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| P/N | 0.4572 | ambiguous | 0.4468 | ambiguous | -0.663 | Destabilizing | 0.998 | D | 0.81 | deleterious | None | None | None | None | N |
| P/Q | 0.237 | likely_benign | 0.2508 | benign | -0.975 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| P/R | 0.2899 | likely_benign | 0.3087 | benign | -0.341 | Destabilizing | 0.998 | D | 0.811 | deleterious | N | 0.47952851 | None | None | N |
| P/S | 0.1787 | likely_benign | 0.1767 | benign | -1.083 | Destabilizing | 0.978 | D | 0.697 | prob.neutral | N | 0.476829585 | None | None | N |
| P/T | 0.1332 | likely_benign | 0.1354 | benign | -1.069 | Destabilizing | 0.997 | D | 0.712 | prob.delet. | N | 0.478014141 | None | None | N |
| P/V | 0.1587 | likely_benign | 0.1735 | benign | -0.908 | Destabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| P/W | 0.6318 | likely_pathogenic | 0.6778 | pathogenic | -1.334 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| P/Y | 0.4513 | ambiguous | 0.4758 | ambiguous | -1.078 | Destabilizing | 0.998 | D | 0.82 | 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.