Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2621 | 8086;8087;8088 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
| N2AB | 2621 | 8086;8087;8088 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
| N2A | 2621 | 8086;8087;8088 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
| N2B | 2575 | 7948;7949;7950 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
| Novex-1 | 2575 | 7948;7949;7950 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
| Novex-2 | 2575 | 7948;7949;7950 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
| Novex-3 | 2621 | 8086;8087;8088 | chr2:178771466;178771465;178771464 | chr2:179636193;179636192;179636191 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs753441258  |
0.255 | 1.0 | N | 0.757 | 0.472 | 0.762034995844 | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 0 | 4.04952E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 3.26477E-04 |
| A/D | rs753441258 |
0.255 | 1.0 | N | 0.757 | 0.472 | 0.762034995844 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/D | rs753441258 |
0.255 | 1.0 | N | 0.757 | 0.472 | 0.762034995844 | gnomAD-4.0.0 | 9.91497E-06 | None | None | None | None | N | None | 0 | 2.50083E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60077E-05 |
| A/V | rs753441258 |
-0.105 | 1.0 | D | 0.666 | 0.361 | 0.640935244609 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.53E-05 | 0 |
| A/V | rs753441258 |
-0.105 | 1.0 | D | 0.666 | 0.361 | 0.640935244609 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs753441258 |
-0.105 | 1.0 | D | 0.666 | 0.361 | 0.640935244609 | gnomAD-4.0.0 | 8.6756E-06 | None | None | None | None | N | None | 0 | 1.66722E-05 | None | 0 | 0 | None | 0 | 0 | 1.10188E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.849 | likely_pathogenic | 0.8384 | pathogenic | -0.788 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| A/D | 0.7329 | likely_pathogenic | 0.698 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.507567176 | None | None | N |
| A/E | 0.6698 | likely_pathogenic | 0.613 | pathogenic | -0.44 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| A/F | 0.7138 | likely_pathogenic | 0.6812 | pathogenic | -0.919 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| A/G | 0.3495 | ambiguous | 0.3559 | ambiguous | -0.444 | Destabilizing | 1.0 | D | 0.637 | neutral | D | 0.58320895 | None | None | N |
| A/H | 0.8656 | likely_pathogenic | 0.8361 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/I | 0.6698 | likely_pathogenic | 0.6474 | pathogenic | -0.333 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| A/K | 0.8618 | likely_pathogenic | 0.8273 | pathogenic | -0.636 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/L | 0.5226 | ambiguous | 0.4892 | ambiguous | -0.333 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| A/M | 0.5911 | likely_pathogenic | 0.5685 | pathogenic | -0.347 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/N | 0.6714 | likely_pathogenic | 0.6294 | pathogenic | -0.33 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| A/P | 0.7576 | likely_pathogenic | 0.7068 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.580122027 | None | None | N |
| A/Q | 0.7189 | likely_pathogenic | 0.6679 | pathogenic | -0.582 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| A/R | 0.7755 | likely_pathogenic | 0.7195 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| A/S | 0.1906 | likely_benign | 0.1804 | benign | -0.583 | Destabilizing | 1.0 | D | 0.628 | neutral | N | 0.506482874 | None | None | N |
| A/T | 0.2987 | likely_benign | 0.2783 | benign | -0.634 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.504387444 | None | None | N |
| A/V | 0.4067 | ambiguous | 0.3775 | ambiguous | -0.307 | Destabilizing | 1.0 | D | 0.666 | neutral | D | 0.578195587 | None | None | N |
| A/W | 0.9583 | likely_pathogenic | 0.9515 | pathogenic | -1.081 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| A/Y | 0.8528 | likely_pathogenic | 0.8262 | pathogenic | -0.712 | Destabilizing | 1.0 | D | 0.741 | 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.