Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15316 | 46171;46172;46173 | chr2:178620575;178620574;178620573 | chr2:179485302;179485301;179485300 |
| N2AB | 13675 | 41248;41249;41250 | chr2:178620575;178620574;178620573 | chr2:179485302;179485301;179485300 |
| N2A | 12748 | 38467;38468;38469 | chr2:178620575;178620574;178620573 | chr2:179485302;179485301;179485300 |
| N2B | 6251 | 18976;18977;18978 | chr2:178620575;178620574;178620573 | chr2:179485302;179485301;179485300 |
| Novex-1 | 6376 | 19351;19352;19353 | chr2:178620575;178620574;178620573 | chr2:179485302;179485301;179485300 |
| Novex-2 | 6443 | 19552;19553;19554 | chr2:178620575;178620574;178620573 | chr2:179485302;179485301;179485300 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs781445105  |
0.141 | 1.0 | N | 0.694 | 0.376 | 0.311691414656 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| K/N | rs781445105 |
0.141 | 1.0 | N | 0.694 | 0.376 | 0.311691414656 | gnomAD-4.0.0 | 1.59663E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86691E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6784 | likely_pathogenic | 0.669 | pathogenic | 0.1 | Stabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| K/C | 0.8964 | likely_pathogenic | 0.8946 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| K/D | 0.6554 | likely_pathogenic | 0.6367 | pathogenic | -0.035 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| K/E | 0.3154 | likely_benign | 0.3004 | benign | -0.036 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | D | 0.564939181 | None | None | N |
| K/F | 0.9312 | likely_pathogenic | 0.9235 | pathogenic | -0.12 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| K/G | 0.4079 | ambiguous | 0.4085 | ambiguous | -0.085 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| K/H | 0.5404 | ambiguous | 0.5133 | ambiguous | -0.307 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| K/I | 0.841 | likely_pathogenic | 0.82 | pathogenic | 0.508 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| K/L | 0.6662 | likely_pathogenic | 0.658 | pathogenic | 0.508 | Stabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| K/M | 0.4604 | ambiguous | 0.4636 | ambiguous | 0.24 | Stabilizing | 1.0 | D | 0.741 | deleterious | D | 0.635337621 | None | None | N |
| K/N | 0.4378 | ambiguous | 0.425 | ambiguous | 0.354 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.504492964 | None | None | N |
| K/P | 0.9505 | likely_pathogenic | 0.9347 | pathogenic | 0.399 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| K/Q | 0.232 | likely_benign | 0.2283 | benign | 0.172 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.592546491 | None | None | N |
| K/R | 0.1296 | likely_benign | 0.1134 | benign | 0.064 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | D | 0.552398235 | None | None | N |
| K/S | 0.6229 | likely_pathogenic | 0.6115 | pathogenic | -0.08 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| K/T | 0.4512 | ambiguous | 0.4204 | ambiguous | 0.055 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.539288192 | None | None | N |
| K/V | 0.7962 | likely_pathogenic | 0.776 | pathogenic | 0.399 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| K/W | 0.9246 | likely_pathogenic | 0.9047 | pathogenic | -0.167 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| K/Y | 0.8123 | likely_pathogenic | 0.7986 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.701 | prob.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.