Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13938 | 42037;42038;42039 | chr2:178635512;178635511;178635510 | chr2:179500239;179500238;179500237 |
| N2AB | 12297 | 37114;37115;37116 | chr2:178635512;178635511;178635510 | chr2:179500239;179500238;179500237 |
| N2A | 11370 | 34333;34334;34335 | chr2:178635512;178635511;178635510 | chr2:179500239;179500238;179500237 |
| N2B | 4873 | 14842;14843;14844 | chr2:178635512;178635511;178635510 | chr2:179500239;179500238;179500237 |
| Novex-1 | 4998 | 15217;15218;15219 | chr2:178635512;178635511;178635510 | chr2:179500239;179500238;179500237 |
| Novex-2 | 5065 | 15418;15419;15420 | chr2:178635512;178635511;178635510 | chr2:179500239;179500238;179500237 |
| 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/V | rs201725483  |
-0.408 | None | N | 0.087 | 0.072 | None | gnomAD-2.1.1 | 3.86E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.58E-05 | 0 |
| M/V | rs201725483 |
-0.408 | None | N | 0.087 | 0.072 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02959E-04 | 0 | 0 |
| M/V | rs201725483 |
-0.408 | None | N | 0.087 | 0.072 | None | gnomAD-4.0.0 | 1.13639E-04 | None | None | None | None | N | None | 1.33636E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.48321E-04 | 0 | 1.12896E-04 |
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 | 0.2021 | likely_benign | 0.2184 | benign | -1.531 | Destabilizing | None | N | 0.38 | neutral | None | None | None | None | N |
| M/C | 0.6856 | likely_pathogenic | 0.7249 | pathogenic | -0.823 | Destabilizing | 0.066 | N | 0.313 | neutral | None | None | None | None | N |
| M/D | 0.6709 | likely_pathogenic | 0.669 | pathogenic | -0.642 | Destabilizing | 0.001 | N | 0.311 | neutral | None | None | None | None | N |
| M/E | 0.3211 | likely_benign | 0.3331 | benign | -0.67 | Destabilizing | 0.001 | N | 0.281 | neutral | None | None | None | None | N |
| M/F | 0.3598 | ambiguous | 0.3618 | ambiguous | -0.93 | Destabilizing | 0.01 | N | 0.254 | neutral | None | None | None | None | N |
| M/G | 0.3244 | likely_benign | 0.3442 | ambiguous | -1.774 | Destabilizing | None | N | 0.153 | neutral | None | None | None | None | N |
| M/H | 0.4925 | ambiguous | 0.5292 | ambiguous | -0.93 | Destabilizing | 0.066 | N | 0.461 | neutral | None | None | None | None | N |
| M/I | 0.3775 | ambiguous | 0.3267 | benign | -0.937 | Destabilizing | None | N | 0.202 | neutral | N | 0.447594833 | None | None | N |
| M/K | 0.2138 | likely_benign | 0.2053 | benign | -0.4 | Destabilizing | 0.001 | N | 0.292 | neutral | N | 0.439845505 | None | None | N |
| M/L | 0.1137 | likely_benign | 0.1055 | benign | -0.937 | Destabilizing | None | N | 0.104 | neutral | N | 0.444922463 | None | None | N |
| M/N | 0.27 | likely_benign | 0.301 | benign | -0.146 | Destabilizing | None | N | 0.175 | neutral | None | None | None | None | N |
| M/P | 0.9506 | likely_pathogenic | 0.9292 | pathogenic | -1.109 | Destabilizing | 0.008 | N | 0.347 | neutral | None | None | None | None | N |
| M/Q | 0.1747 | likely_benign | 0.1939 | benign | -0.341 | Destabilizing | None | N | 0.137 | neutral | None | None | None | None | N |
| M/R | 0.2961 | likely_benign | 0.2609 | benign | 0.166 | Stabilizing | None | N | 0.237 | neutral | N | 0.444866762 | None | None | N |
| M/S | 0.1916 | likely_benign | 0.2129 | benign | -0.648 | Destabilizing | None | N | 0.304 | neutral | None | None | None | None | N |
| M/T | 0.0984 | likely_benign | 0.1034 | benign | -0.58 | Destabilizing | None | N | 0.149 | neutral | N | 0.439285215 | None | None | N |
| M/V | 0.1049 | likely_benign | 0.0938 | benign | -1.109 | Destabilizing | None | N | 0.087 | neutral | N | 0.446740316 | None | None | N |
| M/W | 0.815 | likely_pathogenic | 0.8084 | pathogenic | -0.828 | Destabilizing | 0.176 | N | 0.306 | neutral | None | None | None | None | N |
| M/Y | 0.5898 | likely_pathogenic | 0.6283 | pathogenic | -0.822 | Destabilizing | 0.02 | N | 0.433 | neutral | 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.