Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14172 | 42739;42740;42741 | chr2:178633985;178633984;178633983 | chr2:179498712;179498711;179498710 |
| N2AB | 12531 | 37816;37817;37818 | chr2:178633985;178633984;178633983 | chr2:179498712;179498711;179498710 |
| N2A | 11604 | 35035;35036;35037 | chr2:178633985;178633984;178633983 | chr2:179498712;179498711;179498710 |
| N2B | 5107 | 15544;15545;15546 | chr2:178633985;178633984;178633983 | chr2:179498712;179498711;179498710 |
| Novex-1 | 5232 | 15919;15920;15921 | chr2:178633985;178633984;178633983 | chr2:179498712;179498711;179498710 |
| Novex-2 | 5299 | 16120;16121;16122 | chr2:178633985;178633984;178633983 | chr2:179498712;179498711;179498710 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs2060117158  |
None | 0.002 | D | 0.349 | 0.413 | 0.616247408722 | gnomAD-4.0.0 | 3.18409E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72001E-06 | 0 | 0 |
| V/L | rs748615976 |
-0.879 | 0.002 | D | 0.337 | 0.365 | 0.53586618445 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs748615976 |
-0.879 | 0.002 | D | 0.337 | 0.365 | 0.53586618445 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs748615976 |
-0.879 | 0.002 | D | 0.337 | 0.365 | 0.53586618445 | gnomAD-4.0.0 | 3.84564E-06 | None | None | None | None | N | None | 0 | 5.08854E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4543 | ambiguous | 0.3743 | ambiguous | -1.943 | Destabilizing | 0.002 | N | 0.349 | neutral | D | 0.668657976 | None | None | N |
| V/C | 0.9002 | likely_pathogenic | 0.8917 | pathogenic | -1.029 | Destabilizing | 0.947 | D | 0.754 | deleterious | None | None | None | None | N |
| V/D | 0.9851 | likely_pathogenic | 0.9813 | pathogenic | -2.488 | Highly Destabilizing | 0.7 | D | 0.865 | deleterious | None | None | None | None | N |
| V/E | 0.9732 | likely_pathogenic | 0.9657 | pathogenic | -2.338 | Highly Destabilizing | 0.638 | D | 0.856 | deleterious | D | 0.728102296 | None | None | N |
| V/F | 0.6643 | likely_pathogenic | 0.6593 | pathogenic | -1.332 | Destabilizing | 0.539 | D | 0.784 | deleterious | None | None | None | None | N |
| V/G | 0.7229 | likely_pathogenic | 0.7139 | pathogenic | -2.372 | Highly Destabilizing | 0.468 | N | 0.841 | deleterious | D | 0.547540036 | None | None | N |
| V/H | 0.9908 | likely_pathogenic | 0.9882 | pathogenic | -2.035 | Highly Destabilizing | 0.982 | D | 0.847 | deleterious | None | None | None | None | N |
| V/I | 0.1176 | likely_benign | 0.1022 | benign | -0.771 | Destabilizing | 0.094 | N | 0.627 | neutral | D | 0.551369681 | None | None | N |
| V/K | 0.9778 | likely_pathogenic | 0.9746 | pathogenic | -1.621 | Destabilizing | 0.7 | D | 0.853 | deleterious | None | None | None | None | N |
| V/L | 0.4453 | ambiguous | 0.4115 | ambiguous | -0.771 | Destabilizing | 0.002 | N | 0.337 | neutral | D | 0.600954675 | None | None | N |
| V/M | 0.4713 | ambiguous | 0.3687 | ambiguous | -0.49 | Destabilizing | 0.7 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/N | 0.9651 | likely_pathogenic | 0.947 | pathogenic | -1.695 | Destabilizing | 0.826 | D | 0.85 | deleterious | None | None | None | None | N |
| V/P | 0.8248 | likely_pathogenic | 0.8355 | pathogenic | -1.136 | Destabilizing | 0.7 | D | 0.861 | deleterious | None | None | None | None | N |
| V/Q | 0.9741 | likely_pathogenic | 0.9663 | pathogenic | -1.693 | Destabilizing | 0.826 | D | 0.847 | deleterious | None | None | None | None | N |
| V/R | 0.9647 | likely_pathogenic | 0.9626 | pathogenic | -1.28 | Destabilizing | 0.7 | D | 0.861 | deleterious | None | None | None | None | N |
| V/S | 0.8383 | likely_pathogenic | 0.7613 | pathogenic | -2.186 | Highly Destabilizing | 0.539 | D | 0.844 | deleterious | None | None | None | None | N |
| V/T | 0.5211 | ambiguous | 0.4027 | ambiguous | -1.922 | Destabilizing | 0.25 | N | 0.688 | prob.neutral | None | None | None | None | N |
| V/W | 0.9914 | likely_pathogenic | 0.9907 | pathogenic | -1.781 | Destabilizing | 0.982 | D | 0.844 | deleterious | None | None | None | None | N |
| V/Y | 0.9712 | likely_pathogenic | 0.9728 | pathogenic | -1.402 | Destabilizing | 0.826 | D | 0.769 | 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.