Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29610 | 89053;89054;89055 | chr2:178554519;178554518;178554517 | chr2:179419246;179419245;179419244 |
| N2AB | 27969 | 84130;84131;84132 | chr2:178554519;178554518;178554517 | chr2:179419246;179419245;179419244 |
| N2A | 27042 | 81349;81350;81351 | chr2:178554519;178554518;178554517 | chr2:179419246;179419245;179419244 |
| N2B | 20545 | 61858;61859;61860 | chr2:178554519;178554518;178554517 | chr2:179419246;179419245;179419244 |
| Novex-1 | 20670 | 62233;62234;62235 | chr2:178554519;178554518;178554517 | chr2:179419246;179419245;179419244 |
| Novex-2 | 20737 | 62434;62435;62436 | chr2:178554519;178554518;178554517 | chr2:179419246;179419245;179419244 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs1060500410  |
None | 0.782 | D | 0.817 | 0.533 | 0.672435393608 | 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/D | rs1060500410 |
None | 0.782 | D | 0.817 | 0.533 | 0.672435393608 | gnomAD-4.0.0 | 5.12605E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57272E-06 | 0 | 0 |
| A/T | rs1289495878 |
-1.791 | 0.505 | D | 0.73 | 0.47 | 0.489104616352 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/T | rs1289495878 |
-1.791 | 0.505 | D | 0.73 | 0.47 | 0.489104616352 | gnomAD-4.0.0 | 3.18407E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86681E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8307 | likely_pathogenic | 0.8471 | pathogenic | -1.765 | Destabilizing | 0.991 | D | 0.714 | prob.delet. | None | None | None | None | N |
| A/D | 0.9918 | likely_pathogenic | 0.9925 | pathogenic | -2.744 | Highly Destabilizing | 0.782 | D | 0.817 | deleterious | D | 0.55626706 | None | None | N |
| A/E | 0.9904 | likely_pathogenic | 0.9923 | pathogenic | -2.51 | Highly Destabilizing | 0.906 | D | 0.791 | deleterious | None | None | None | None | N |
| A/F | 0.9887 | likely_pathogenic | 0.9909 | pathogenic | -0.727 | Destabilizing | 0.967 | D | 0.842 | deleterious | None | None | None | None | N |
| A/G | 0.1248 | likely_benign | 0.1234 | benign | -2.327 | Highly Destabilizing | None | N | 0.373 | neutral | N | 0.502661857 | None | None | N |
| A/H | 0.9954 | likely_pathogenic | 0.9964 | pathogenic | -2.201 | Highly Destabilizing | 0.991 | D | 0.835 | deleterious | None | None | None | None | N |
| A/I | 0.9781 | likely_pathogenic | 0.9836 | pathogenic | -0.712 | Destabilizing | 0.906 | D | 0.781 | deleterious | None | None | None | None | N |
| A/K | 0.998 | likely_pathogenic | 0.9985 | pathogenic | -1.516 | Destabilizing | 0.826 | D | 0.785 | deleterious | None | None | None | None | N |
| A/L | 0.9246 | likely_pathogenic | 0.9421 | pathogenic | -0.712 | Destabilizing | 0.733 | D | 0.797 | deleterious | None | None | None | None | N |
| A/M | 0.9649 | likely_pathogenic | 0.9736 | pathogenic | -1.216 | Destabilizing | 0.991 | D | 0.763 | deleterious | None | None | None | None | N |
| A/N | 0.9809 | likely_pathogenic | 0.985 | pathogenic | -1.961 | Destabilizing | 0.826 | D | 0.824 | deleterious | None | None | None | None | N |
| A/P | 0.608 | likely_pathogenic | 0.7615 | pathogenic | -1.083 | Destabilizing | 0.879 | D | 0.787 | deleterious | D | 0.538327389 | None | None | N |
| A/Q | 0.9871 | likely_pathogenic | 0.99 | pathogenic | -1.647 | Destabilizing | 0.906 | D | 0.757 | deleterious | None | None | None | None | N |
| A/R | 0.9924 | likely_pathogenic | 0.9941 | pathogenic | -1.61 | Destabilizing | 0.906 | D | 0.781 | deleterious | None | None | None | None | N |
| A/S | 0.3534 | ambiguous | 0.3748 | ambiguous | -2.322 | Highly Destabilizing | 0.338 | N | 0.646 | neutral | N | 0.498165179 | None | None | N |
| A/T | 0.8157 | likely_pathogenic | 0.8521 | pathogenic | -1.985 | Destabilizing | 0.505 | D | 0.73 | prob.delet. | D | 0.529498617 | None | None | N |
| A/V | 0.8858 | likely_pathogenic | 0.9105 | pathogenic | -1.083 | Destabilizing | 0.674 | D | 0.703 | prob.neutral | D | 0.536045983 | None | None | N |
| A/W | 0.9977 | likely_pathogenic | 0.9983 | pathogenic | -1.337 | Destabilizing | 0.991 | D | 0.838 | deleterious | None | None | None | None | N |
| A/Y | 0.9932 | likely_pathogenic | 0.995 | pathogenic | -1.109 | Destabilizing | 0.967 | D | 0.851 | 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.