Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32964 | 99115;99116;99117 | chr2:178539045;178539044;178539043 | chr2:179403772;179403771;179403770 |
| N2AB | 31323 | 94192;94193;94194 | chr2:178539045;178539044;178539043 | chr2:179403772;179403771;179403770 |
| N2A | 30396 | 91411;91412;91413 | chr2:178539045;178539044;178539043 | chr2:179403772;179403771;179403770 |
| N2B | 23899 | 71920;71921;71922 | chr2:178539045;178539044;178539043 | chr2:179403772;179403771;179403770 |
| Novex-1 | 24024 | 72295;72296;72297 | chr2:178539045;178539044;178539043 | chr2:179403772;179403771;179403770 |
| Novex-2 | 24091 | 72496;72497;72498 | chr2:178539045;178539044;178539043 | chr2:179403772;179403771;179403770 |
| 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/A | rs750948702  |
None | 0.996 | D | 0.591 | 0.482 | 0.415820034956 | gnomAD-4.0.0 | 1.16318E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52916E-05 | 0 | 0 |
| P/S | rs750948702 |
-1.161 | 0.998 | D | 0.676 | 0.521 | 0.445614145163 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/S | rs750948702 |
-1.161 | 0.998 | D | 0.676 | 0.521 | 0.445614145163 | gnomAD-4.0.0 | 2.7369E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59802E-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 | 0.1021 | likely_benign | 0.1189 | benign | -0.765 | Destabilizing | 0.996 | D | 0.591 | neutral | D | 0.524861348 | None | None | N |
| P/C | 0.7555 | likely_pathogenic | 0.7838 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| P/D | 0.7627 | likely_pathogenic | 0.8103 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| P/E | 0.41 | ambiguous | 0.4539 | ambiguous | -0.854 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| P/F | 0.8422 | likely_pathogenic | 0.8939 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| P/G | 0.4993 | ambiguous | 0.541 | ambiguous | -0.925 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| P/H | 0.4769 | ambiguous | 0.544 | ambiguous | -0.496 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.497559749 | None | None | N |
| P/I | 0.5928 | likely_pathogenic | 0.6741 | pathogenic | -0.484 | Destabilizing | 0.999 | D | 0.764 | deleterious | None | None | None | None | N |
| P/K | 0.6048 | likely_pathogenic | 0.6549 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| P/L | 0.2666 | likely_benign | 0.3416 | ambiguous | -0.484 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | N | 0.497306259 | None | None | N |
| P/M | 0.5464 | ambiguous | 0.6318 | pathogenic | -0.271 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| P/N | 0.5756 | likely_pathogenic | 0.6495 | pathogenic | -0.241 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| P/Q | 0.2838 | likely_benign | 0.3237 | benign | -0.561 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| P/R | 0.4546 | ambiguous | 0.5002 | ambiguous | 0.023 | Stabilizing | 0.999 | D | 0.741 | deleterious | N | 0.501167373 | None | None | N |
| P/S | 0.2021 | likely_benign | 0.24 | benign | -0.592 | Destabilizing | 0.998 | D | 0.676 | prob.neutral | D | 0.535926491 | None | None | N |
| P/T | 0.1539 | likely_benign | 0.1938 | benign | -0.618 | Destabilizing | 0.884 | D | 0.392 | neutral | D | 0.531886108 | None | None | N |
| P/V | 0.3949 | ambiguous | 0.4652 | ambiguous | -0.542 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| P/W | 0.9156 | likely_pathogenic | 0.9376 | pathogenic | -1.068 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| P/Y | 0.8226 | likely_pathogenic | 0.8687 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.792 | 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.