Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15007 | 45244;45245;45246 | chr2:178621903;178621902;178621901 | chr2:179486630;179486629;179486628 |
| N2AB | 13366 | 40321;40322;40323 | chr2:178621903;178621902;178621901 | chr2:179486630;179486629;179486628 |
| N2A | 12439 | 37540;37541;37542 | chr2:178621903;178621902;178621901 | chr2:179486630;179486629;179486628 |
| N2B | 5942 | 18049;18050;18051 | chr2:178621903;178621902;178621901 | chr2:179486630;179486629;179486628 |
| Novex-1 | 6067 | 18424;18425;18426 | chr2:178621903;178621902;178621901 | chr2:179486630;179486629;179486628 |
| Novex-2 | 6134 | 18625;18626;18627 | chr2:178621903;178621902;178621901 | chr2:179486630;179486629;179486628 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs1356461359  |
0.038 | 1.0 | D | 0.787 | 0.834 | 0.691146523942 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1356461359 |
0.038 | 1.0 | D | 0.787 | 0.834 | 0.691146523942 | gnomAD-4.0.0 | 3.42441E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.06817E-05 | None | 0 | 0 | 1.80006E-06 | 1.16031E-05 | 0 |
| D/Y | rs1356461359 |
0.614 | 1.0 | D | 0.801 | 0.821 | 0.895427483255 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1356461359 |
0.614 | 1.0 | D | 0.801 | 0.821 | 0.895427483255 | gnomAD-4.0.0 | 6.84882E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16031E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9717 | likely_pathogenic | 0.9637 | pathogenic | 0.435 | Stabilizing | 1.0 | D | 0.808 | deleterious | D | 0.76415599 | None | None | N |
| D/C | 0.994 | likely_pathogenic | 0.9931 | pathogenic | 0.266 | Stabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| D/E | 0.894 | likely_pathogenic | 0.8883 | pathogenic | -0.667 | Destabilizing | 1.0 | D | 0.553 | neutral | D | 0.744095646 | None | None | N |
| D/F | 0.9969 | likely_pathogenic | 0.9962 | pathogenic | 1.086 | Stabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| D/G | 0.9736 | likely_pathogenic | 0.9669 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.764 | deleterious | D | 0.797755377 | None | None | N |
| D/H | 0.9787 | likely_pathogenic | 0.9752 | pathogenic | 0.624 | Stabilizing | 1.0 | D | 0.787 | deleterious | D | 0.742349246 | None | None | N |
| D/I | 0.9948 | likely_pathogenic | 0.9933 | pathogenic | 1.691 | Stabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| D/K | 0.9909 | likely_pathogenic | 0.9899 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| D/L | 0.9923 | likely_pathogenic | 0.9903 | pathogenic | 1.691 | Stabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| D/M | 0.9958 | likely_pathogenic | 0.9945 | pathogenic | 2.039 | Highly Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| D/N | 0.8625 | likely_pathogenic | 0.847 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.74452345 | None | None | N |
| D/P | 0.9989 | likely_pathogenic | 0.9986 | pathogenic | 1.303 | Stabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| D/Q | 0.9817 | likely_pathogenic | 0.9804 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| D/R | 0.9929 | likely_pathogenic | 0.9911 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| D/S | 0.9352 | likely_pathogenic | 0.9235 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/T | 0.9807 | likely_pathogenic | 0.976 | pathogenic | -0.586 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| D/V | 0.9838 | likely_pathogenic | 0.9787 | pathogenic | 1.303 | Stabilizing | 1.0 | D | 0.818 | deleterious | D | 0.797724501 | None | None | N |
| D/W | 0.9993 | likely_pathogenic | 0.9989 | pathogenic | 1.061 | Stabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| D/Y | 0.9781 | likely_pathogenic | 0.9716 | pathogenic | 1.316 | Stabilizing | 1.0 | D | 0.801 | deleterious | D | 0.763474586 | 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.