Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18295 | 55108;55109;55110 | chr2:178602519;178602518;178602517 | chr2:179467246;179467245;179467244 |
| N2AB | 16654 | 50185;50186;50187 | chr2:178602519;178602518;178602517 | chr2:179467246;179467245;179467244 |
| N2A | 15727 | 47404;47405;47406 | chr2:178602519;178602518;178602517 | chr2:179467246;179467245;179467244 |
| N2B | 9230 | 27913;27914;27915 | chr2:178602519;178602518;178602517 | chr2:179467246;179467245;179467244 |
| Novex-1 | 9355 | 28288;28289;28290 | chr2:178602519;178602518;178602517 | chr2:179467246;179467245;179467244 |
| Novex-2 | 9422 | 28489;28490;28491 | chr2:178602519;178602518;178602517 | chr2:179467246;179467245;179467244 |
| 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/S | rs1162176452  |
-1.749 | 0.885 | N | 0.597 | 0.318 | 0.358540694251 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| P/S | rs1162176452 |
-1.749 | 0.885 | N | 0.597 | 0.318 | 0.358540694251 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs1162176452 |
-1.749 | 0.885 | N | 0.597 | 0.318 | 0.358540694251 | gnomAD-4.0.0 | 5.15904E-06 | None | None | None | None | N | None | 1.69653E-05 | 1.71662E-05 | None | 0 | 0 | None | 0 | 0 | 4.8157E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.089 | likely_benign | 0.0758 | benign | -1.617 | Destabilizing | 0.17 | N | 0.332 | neutral | D | 0.522274042 | None | None | N |
| P/C | 0.5663 | likely_pathogenic | 0.4655 | ambiguous | -1.048 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| P/D | 0.7358 | likely_pathogenic | 0.6934 | pathogenic | -1.786 | Destabilizing | 0.986 | D | 0.656 | neutral | None | None | None | None | N |
| P/E | 0.3497 | ambiguous | 0.3258 | benign | -1.725 | Destabilizing | 0.91 | D | 0.613 | neutral | None | None | None | None | N |
| P/F | 0.6328 | likely_pathogenic | 0.522 | ambiguous | -1.174 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| P/G | 0.4724 | ambiguous | 0.4179 | ambiguous | -1.972 | Destabilizing | 0.953 | D | 0.623 | neutral | None | None | None | None | N |
| P/H | 0.3439 | ambiguous | 0.273 | benign | -1.473 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | N | 0.507624337 | None | None | N |
| P/I | 0.2659 | likely_benign | 0.2198 | benign | -0.712 | Destabilizing | 0.993 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/K | 0.257 | likely_benign | 0.2221 | benign | -1.48 | Destabilizing | 0.128 | N | 0.318 | neutral | None | None | None | None | N |
| P/L | 0.1367 | likely_benign | 0.1105 | benign | -0.712 | Destabilizing | 0.982 | D | 0.677 | prob.neutral | N | 0.511890298 | None | None | N |
| P/M | 0.2906 | likely_benign | 0.2382 | benign | -0.598 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | N |
| P/N | 0.5714 | likely_pathogenic | 0.5118 | ambiguous | -1.384 | Destabilizing | 0.986 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/Q | 0.197 | likely_benign | 0.1616 | benign | -1.473 | Destabilizing | 0.986 | D | 0.683 | prob.neutral | None | None | None | None | N |
| P/R | 0.2217 | likely_benign | 0.1752 | benign | -0.995 | Destabilizing | 0.964 | D | 0.708 | prob.delet. | N | 0.521834112 | None | None | N |
| P/S | 0.2272 | likely_benign | 0.1958 | benign | -1.851 | Destabilizing | 0.885 | D | 0.597 | neutral | N | 0.488670708 | None | None | N |
| P/T | 0.1708 | likely_benign | 0.1432 | benign | -1.671 | Destabilizing | 0.982 | D | 0.655 | neutral | N | 0.49896383 | None | None | N |
| P/V | 0.1759 | likely_benign | 0.148 | benign | -0.982 | Destabilizing | 0.986 | D | 0.649 | neutral | None | None | None | None | N |
| P/W | 0.8431 | likely_pathogenic | 0.7481 | pathogenic | -1.43 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| P/Y | 0.5818 | likely_pathogenic | 0.4682 | ambiguous | -1.122 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | 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.