Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22279 | 67060;67061;67062 | chr2:178580544;178580543;178580542 | chr2:179445271;179445270;179445269 |
| N2AB | 20638 | 62137;62138;62139 | chr2:178580544;178580543;178580542 | chr2:179445271;179445270;179445269 |
| N2A | 19711 | 59356;59357;59358 | chr2:178580544;178580543;178580542 | chr2:179445271;179445270;179445269 |
| N2B | 13214 | 39865;39866;39867 | chr2:178580544;178580543;178580542 | chr2:179445271;179445270;179445269 |
| Novex-1 | 13339 | 40240;40241;40242 | chr2:178580544;178580543;178580542 | chr2:179445271;179445270;179445269 |
| Novex-2 | 13406 | 40441;40442;40443 | chr2:178580544;178580543;178580542 | chr2:179445271;179445270;179445269 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | rs758406122  |
-1.123 | 0.773 | N | 0.732 | 0.441 | 0.564133873757 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 6.68449E-04 |
| M/R | rs758406122 |
-1.123 | 0.773 | N | 0.732 | 0.441 | 0.564133873757 | gnomAD-4.0.0 | 6.162E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.04239E-03 | 0 | 0 | 4.97529E-05 |
| M/V | rs780268398 |
-1.596 | 0.015 | N | 0.435 | 0.233 | 0.303123707472 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.69186E-04 | None | 0 | None | 0 | 0 | 1.67112E-04 |
| M/V | rs780268398 |
-1.596 | 0.015 | N | 0.435 | 0.233 | 0.303123707472 | gnomAD-4.0.0 | 4.10802E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.26653E-04 | None | 0 | 0 | 0 | 0 | 1.65848E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8857 | likely_pathogenic | 0.8709 | pathogenic | -2.996 | Highly Destabilizing | 0.207 | N | 0.575 | neutral | None | None | None | None | N |
| M/C | 0.9216 | likely_pathogenic | 0.9121 | pathogenic | -2.658 | Highly Destabilizing | 0.981 | D | 0.701 | prob.neutral | None | None | None | None | N |
| M/D | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -2.072 | Highly Destabilizing | 0.932 | D | 0.751 | deleterious | None | None | None | None | N |
| M/E | 0.9921 | likely_pathogenic | 0.9913 | pathogenic | -1.87 | Destabilizing | 0.818 | D | 0.729 | prob.delet. | None | None | None | None | N |
| M/F | 0.7576 | likely_pathogenic | 0.7008 | pathogenic | -1.434 | Destabilizing | 0.241 | N | 0.647 | neutral | None | None | None | None | N |
| M/G | 0.9752 | likely_pathogenic | 0.9705 | pathogenic | -3.464 | Highly Destabilizing | 0.563 | D | 0.723 | prob.delet. | None | None | None | None | N |
| M/H | 0.9955 | likely_pathogenic | 0.9942 | pathogenic | -2.544 | Highly Destabilizing | 0.981 | D | 0.691 | prob.neutral | None | None | None | None | N |
| M/I | 0.8057 | likely_pathogenic | 0.7519 | pathogenic | -1.644 | Destabilizing | 0.001 | N | 0.263 | neutral | N | 0.421842397 | None | None | N |
| M/K | 0.9801 | likely_pathogenic | 0.9774 | pathogenic | -1.873 | Destabilizing | 0.492 | N | 0.675 | prob.neutral | N | 0.457792028 | None | None | N |
| M/L | 0.2187 | likely_benign | 0.1818 | benign | -1.644 | Destabilizing | None | N | 0.188 | neutral | N | 0.367295836 | None | None | N |
| M/N | 0.9929 | likely_pathogenic | 0.9917 | pathogenic | -2.122 | Highly Destabilizing | 0.932 | D | 0.726 | prob.delet. | None | None | None | None | N |
| M/P | 0.9972 | likely_pathogenic | 0.9957 | pathogenic | -2.078 | Highly Destabilizing | 0.932 | D | 0.727 | prob.delet. | None | None | None | None | N |
| M/Q | 0.9632 | likely_pathogenic | 0.9596 | pathogenic | -1.922 | Destabilizing | 0.932 | D | 0.69 | prob.neutral | None | None | None | None | N |
| M/R | 0.9838 | likely_pathogenic | 0.9793 | pathogenic | -1.634 | Destabilizing | 0.773 | D | 0.732 | prob.delet. | N | 0.508213375 | None | None | N |
| M/S | 0.9686 | likely_pathogenic | 0.9676 | pathogenic | -2.792 | Highly Destabilizing | 0.563 | D | 0.642 | neutral | None | None | None | None | N |
| M/T | 0.9382 | likely_pathogenic | 0.9253 | pathogenic | -2.454 | Highly Destabilizing | 0.324 | N | 0.646 | neutral | N | 0.478063826 | None | None | N |
| M/V | 0.3094 | likely_benign | 0.2592 | benign | -2.078 | Highly Destabilizing | 0.015 | N | 0.435 | neutral | N | 0.400866905 | None | None | N |
| M/W | 0.9927 | likely_pathogenic | 0.989 | pathogenic | -1.49 | Destabilizing | 0.981 | D | 0.687 | prob.neutral | None | None | None | None | N |
| M/Y | 0.981 | likely_pathogenic | 0.9764 | pathogenic | -1.626 | Destabilizing | 0.818 | D | 0.74 | 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.