Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16636 | 50131;50132;50133 | chr2:178612815;178612814;178612813 | chr2:179477542;179477541;179477540 |
| N2AB | 14995 | 45208;45209;45210 | chr2:178612815;178612814;178612813 | chr2:179477542;179477541;179477540 |
| N2A | 14068 | 42427;42428;42429 | chr2:178612815;178612814;178612813 | chr2:179477542;179477541;179477540 |
| N2B | 7571 | 22936;22937;22938 | chr2:178612815;178612814;178612813 | chr2:179477542;179477541;179477540 |
| Novex-1 | 7696 | 23311;23312;23313 | chr2:178612815;178612814;178612813 | chr2:179477542;179477541;179477540 |
| Novex-2 | 7763 | 23512;23513;23514 | chr2:178612815;178612814;178612813 | chr2:179477542;179477541;179477540 |
| 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/H | rs775947694  |
-1.261 | 1.0 | D | 0.809 | 0.524 | 0.657488933047 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| P/H | rs775947694 |
-1.261 | 1.0 | D | 0.809 | 0.524 | 0.657488933047 | gnomAD-4.0.0 | 3.42389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.80316E-05 | 0 |
| P/R | None | None | 1.0 | D | 0.843 | 0.542 | 0.637538100058 | gnomAD-4.0.0 | 6.84779E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99899E-07 | 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 | 0.1355 | likely_benign | 0.1493 | benign | -1.646 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.549441325 | None | None | N |
| P/C | 0.8501 | likely_pathogenic | 0.8836 | pathogenic | -1.111 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| P/D | 0.9119 | likely_pathogenic | 0.9462 | pathogenic | -2.065 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| P/E | 0.8271 | likely_pathogenic | 0.8832 | pathogenic | -2.098 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| P/F | 0.8427 | likely_pathogenic | 0.868 | pathogenic | -1.439 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| P/G | 0.6879 | likely_pathogenic | 0.737 | pathogenic | -1.913 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| P/H | 0.7567 | likely_pathogenic | 0.8304 | pathogenic | -1.392 | Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.645645659 | None | None | N |
| P/I | 0.7267 | likely_pathogenic | 0.7738 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| P/K | 0.9013 | likely_pathogenic | 0.9455 | pathogenic | -1.315 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| P/L | 0.5151 | ambiguous | 0.5836 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.661134425 | None | None | N |
| P/M | 0.7845 | likely_pathogenic | 0.8164 | pathogenic | -0.738 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| P/N | 0.8896 | likely_pathogenic | 0.9266 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| P/Q | 0.75 | likely_pathogenic | 0.8212 | pathogenic | -1.422 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| P/R | 0.8309 | likely_pathogenic | 0.899 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.624472377 | None | None | N |
| P/S | 0.429 | ambiguous | 0.521 | ambiguous | -1.533 | Destabilizing | 1.0 | D | 0.75 | deleterious | D | 0.6124581 | None | None | N |
| P/T | 0.4851 | ambiguous | 0.5713 | pathogenic | -1.479 | Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.675343318 | None | None | N |
| P/V | 0.5749 | likely_pathogenic | 0.6261 | pathogenic | -1.193 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| P/W | 0.9336 | likely_pathogenic | 0.9521 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/Y | 0.8488 | likely_pathogenic | 0.8887 | pathogenic | -1.321 | Destabilizing | 1.0 | D | 0.849 | 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.