Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15261 | 46006;46007;46008 | chr2:178620829;178620828;178620827 | chr2:179485556;179485555;179485554 |
| N2AB | 13620 | 41083;41084;41085 | chr2:178620829;178620828;178620827 | chr2:179485556;179485555;179485554 |
| N2A | 12693 | 38302;38303;38304 | chr2:178620829;178620828;178620827 | chr2:179485556;179485555;179485554 |
| N2B | 6196 | 18811;18812;18813 | chr2:178620829;178620828;178620827 | chr2:179485556;179485555;179485554 |
| Novex-1 | 6321 | 19186;19187;19188 | chr2:178620829;178620828;178620827 | chr2:179485556;179485555;179485554 |
| Novex-2 | 6388 | 19387;19388;19389 | chr2:178620829;178620828;178620827 | chr2:179485556;179485555;179485554 |
| 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/D | rs978618827  |
-2.158 | 0.901 | D | 0.777 | 0.374 | 0.770231283977 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| V/D | rs978618827 |
-2.158 | 0.901 | D | 0.777 | 0.374 | 0.770231283977 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78469E-04 |
| V/D | rs978618827 |
-2.158 | 0.901 | D | 0.777 | 0.374 | 0.770231283977 | gnomAD-4.0.0 | 7.4407E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.30579E-04 | 5.9363E-06 | 0 | 4.80677E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3103 | likely_benign | 0.3218 | benign | -1.741 | Destabilizing | 0.349 | N | 0.491 | neutral | D | 0.553415985 | None | None | N |
| V/C | 0.8121 | likely_pathogenic | 0.7935 | pathogenic | -1.067 | Destabilizing | 0.996 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/D | 0.6123 | likely_pathogenic | 0.5945 | pathogenic | -2.141 | Highly Destabilizing | 0.901 | D | 0.777 | deleterious | D | 0.535748121 | None | None | N |
| V/E | 0.4549 | ambiguous | 0.4575 | ambiguous | -2.086 | Highly Destabilizing | 0.923 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/F | 0.2122 | likely_benign | 0.2275 | benign | -1.243 | Destabilizing | 0.901 | D | 0.709 | prob.delet. | D | 0.540958484 | None | None | N |
| V/G | 0.3825 | ambiguous | 0.3756 | ambiguous | -2.118 | Highly Destabilizing | 0.901 | D | 0.741 | deleterious | D | 0.555289323 | None | None | N |
| V/H | 0.6482 | likely_pathogenic | 0.6492 | pathogenic | -1.853 | Destabilizing | 0.996 | D | 0.76 | deleterious | None | None | None | None | N |
| V/I | 0.0843 | likely_benign | 0.0899 | benign | -0.764 | Destabilizing | 0.008 | N | 0.201 | neutral | N | 0.506751016 | None | None | N |
| V/K | 0.4932 | ambiguous | 0.4821 | ambiguous | -1.485 | Destabilizing | 0.923 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/L | 0.258 | likely_benign | 0.2778 | benign | -0.764 | Destabilizing | 0.156 | N | 0.433 | neutral | N | 0.50957101 | None | None | N |
| V/M | 0.2077 | likely_benign | 0.2363 | benign | -0.514 | Destabilizing | 0.923 | D | 0.559 | neutral | None | None | None | None | N |
| V/N | 0.3678 | ambiguous | 0.3698 | ambiguous | -1.369 | Destabilizing | 0.923 | D | 0.787 | deleterious | None | None | None | None | N |
| V/P | 0.958 | likely_pathogenic | 0.9478 | pathogenic | -1.059 | Destabilizing | 0.961 | D | 0.747 | deleterious | None | None | None | None | N |
| V/Q | 0.4161 | ambiguous | 0.417 | ambiguous | -1.474 | Destabilizing | 0.961 | D | 0.75 | deleterious | None | None | None | None | N |
| V/R | 0.4115 | ambiguous | 0.3847 | ambiguous | -1.036 | Destabilizing | 0.923 | D | 0.787 | deleterious | None | None | None | None | N |
| V/S | 0.313 | likely_benign | 0.3136 | benign | -1.85 | Destabilizing | 0.858 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/T | 0.2203 | likely_benign | 0.2355 | benign | -1.693 | Destabilizing | 0.024 | N | 0.288 | neutral | None | None | None | None | N |
| V/W | 0.8928 | likely_pathogenic | 0.8936 | pathogenic | -1.617 | Destabilizing | 0.996 | D | 0.728 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6469 | likely_pathogenic | 0.644 | pathogenic | -1.306 | Destabilizing | 0.961 | D | 0.714 | prob.delet. | 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.