Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31345 | 94258;94259;94260 | chr2:178547593;178547592;178547591 | chr2:179412320;179412319;179412318 |
| N2AB | 29704 | 89335;89336;89337 | chr2:178547593;178547592;178547591 | chr2:179412320;179412319;179412318 |
| N2A | 28777 | 86554;86555;86556 | chr2:178547593;178547592;178547591 | chr2:179412320;179412319;179412318 |
| N2B | 22280 | 67063;67064;67065 | chr2:178547593;178547592;178547591 | chr2:179412320;179412319;179412318 |
| Novex-1 | 22405 | 67438;67439;67440 | chr2:178547593;178547592;178547591 | chr2:179412320;179412319;179412318 |
| Novex-2 | 22472 | 67639;67640;67641 | chr2:178547593;178547592;178547591 | chr2:179412320;179412319;179412318 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1297026884  |
None | 1.0 | N | 0.687 | 0.425 | 0.684588293173 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | rs756013336 |
-1.511 | 0.993 | N | 0.409 | 0.235 | 0.545389625809 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs756013336 |
-1.511 | 0.993 | N | 0.409 | 0.235 | 0.545389625809 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs756013336 |
-1.511 | 0.993 | N | 0.409 | 0.235 | 0.545389625809 | gnomAD-4.0.0 | 6.81629E-06 | None | None | None | None | N | None | 5.33846E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08548E-06 | 1.09789E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8482 | likely_pathogenic | 0.8106 | pathogenic | -2.525 | Highly Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| I/C | 0.9316 | likely_pathogenic | 0.9069 | pathogenic | -2.134 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/D | 0.9939 | likely_pathogenic | 0.9918 | pathogenic | -2.924 | Highly Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/E | 0.9811 | likely_pathogenic | 0.9747 | pathogenic | -2.816 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/F | 0.6737 | likely_pathogenic | 0.5853 | pathogenic | -1.705 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/G | 0.9863 | likely_pathogenic | 0.981 | pathogenic | -2.93 | Highly Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/H | 0.9445 | likely_pathogenic | 0.915 | pathogenic | -2.077 | Highly Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| I/K | 0.9268 | likely_pathogenic | 0.9119 | pathogenic | -1.93 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.474656786 | None | None | N |
| I/L | 0.4443 | ambiguous | 0.4187 | ambiguous | -1.402 | Destabilizing | 0.993 | D | 0.399 | neutral | N | 0.463909592 | None | None | N |
| I/M | 0.3679 | ambiguous | 0.3336 | benign | -1.408 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.496056405 | None | None | N |
| I/N | 0.9228 | likely_pathogenic | 0.8972 | pathogenic | -2.092 | Highly Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/P | 0.9962 | likely_pathogenic | 0.9962 | pathogenic | -1.754 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/Q | 0.9449 | likely_pathogenic | 0.9272 | pathogenic | -2.194 | Highly Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| I/R | 0.8633 | likely_pathogenic | 0.8351 | pathogenic | -1.345 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.468869888 | None | None | N |
| I/S | 0.8468 | likely_pathogenic | 0.8052 | pathogenic | -2.725 | Highly Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/T | 0.5622 | ambiguous | 0.4928 | ambiguous | -2.498 | Highly Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.48167264 | None | None | N |
| I/V | 0.1123 | likely_benign | 0.105 | benign | -1.754 | Destabilizing | 0.993 | D | 0.409 | neutral | N | 0.459739929 | None | None | N |
| I/W | 0.9716 | likely_pathogenic | 0.9548 | pathogenic | -1.9 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/Y | 0.9253 | likely_pathogenic | 0.8867 | pathogenic | -1.69 | Destabilizing | 1.0 | D | 0.737 | 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.