Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18802 | 56629;56630;56631 | chr2:178599389;178599388;178599387 | chr2:179464116;179464115;179464114 |
| N2AB | 17161 | 51706;51707;51708 | chr2:178599389;178599388;178599387 | chr2:179464116;179464115;179464114 |
| N2A | 16234 | 48925;48926;48927 | chr2:178599389;178599388;178599387 | chr2:179464116;179464115;179464114 |
| N2B | 9737 | 29434;29435;29436 | chr2:178599389;178599388;178599387 | chr2:179464116;179464115;179464114 |
| Novex-1 | 9862 | 29809;29810;29811 | chr2:178599389;178599388;178599387 | chr2:179464116;179464115;179464114 |
| Novex-2 | 9929 | 30010;30011;30012 | chr2:178599389;178599388;178599387 | chr2:179464116;179464115;179464114 |
| 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/I | rs2052669056  |
None | 0.01 | N | 0.255 | 0.163 | 0.299770980665 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| M/I | rs2052669056 |
None | 0.01 | N | 0.255 | 0.163 | 0.299770980665 | gnomAD-4.0.0 | 6.95705E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.07031E-07 | 0 | 0 |
| M/T | rs541240948 |
None | 0.912 | N | 0.709 | 0.377 | 0.623114596716 | gnomAD-4.0.0 | 1.65458E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.5606E-05 | 0 |
| M/V | None | None | 0.166 | N | 0.431 | 0.231 | 0.361160317528 | 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 |
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 | 0.8053 | likely_pathogenic | 0.8184 | pathogenic | -1.819 | Destabilizing | 0.737 | D | 0.591 | neutral | None | None | None | None | N |
| M/C | 0.8306 | likely_pathogenic | 0.797 | pathogenic | -2.38 | Highly Destabilizing | 0.993 | D | 0.773 | deleterious | None | None | None | None | N |
| M/D | 0.9979 | likely_pathogenic | 0.9976 | pathogenic | -1.877 | Destabilizing | 0.993 | D | 0.801 | deleterious | None | None | None | None | N |
| M/E | 0.978 | likely_pathogenic | 0.9761 | pathogenic | -1.6 | Destabilizing | 0.977 | D | 0.757 | deleterious | None | None | None | None | N |
| M/F | 0.6549 | likely_pathogenic | 0.6617 | pathogenic | -0.453 | Destabilizing | 0.932 | D | 0.665 | neutral | None | None | None | None | N |
| M/G | 0.9701 | likely_pathogenic | 0.9701 | pathogenic | -2.342 | Highly Destabilizing | 0.977 | D | 0.753 | deleterious | None | None | None | None | N |
| M/H | 0.9776 | likely_pathogenic | 0.9746 | pathogenic | -2.265 | Highly Destabilizing | 0.998 | D | 0.768 | deleterious | None | None | None | None | N |
| M/I | 0.3511 | ambiguous | 0.3722 | ambiguous | -0.303 | Destabilizing | 0.01 | N | 0.255 | neutral | N | 0.326742867 | None | None | N |
| M/K | 0.9013 | likely_pathogenic | 0.8859 | pathogenic | -0.994 | Destabilizing | 0.969 | D | 0.733 | prob.delet. | N | 0.518900089 | None | None | N |
| M/L | 0.208 | likely_benign | 0.2375 | benign | -0.303 | Destabilizing | 0.166 | N | 0.347 | neutral | N | 0.399683187 | None | None | N |
| M/N | 0.9784 | likely_pathogenic | 0.9755 | pathogenic | -1.542 | Destabilizing | 0.993 | D | 0.799 | deleterious | None | None | None | None | N |
| M/P | 0.9982 | likely_pathogenic | 0.9985 | pathogenic | -0.791 | Destabilizing | 0.993 | D | 0.798 | deleterious | None | None | None | None | N |
| M/Q | 0.8982 | likely_pathogenic | 0.8859 | pathogenic | -1.097 | Destabilizing | 0.993 | D | 0.735 | prob.delet. | None | None | None | None | N |
| M/R | 0.9236 | likely_pathogenic | 0.916 | pathogenic | -1.448 | Destabilizing | 0.991 | D | 0.811 | deleterious | N | 0.518900089 | None | None | N |
| M/S | 0.948 | likely_pathogenic | 0.9467 | pathogenic | -2.052 | Highly Destabilizing | 0.977 | D | 0.713 | prob.delet. | None | None | None | None | N |
| M/T | 0.8561 | likely_pathogenic | 0.8627 | pathogenic | -1.622 | Destabilizing | 0.912 | D | 0.709 | prob.delet. | N | 0.488923899 | None | None | N |
| M/V | 0.1415 | likely_benign | 0.1462 | benign | -0.791 | Destabilizing | 0.166 | N | 0.431 | neutral | N | 0.36718398 | None | None | N |
| M/W | 0.9653 | likely_pathogenic | 0.9663 | pathogenic | -0.821 | Destabilizing | 0.998 | D | 0.75 | deleterious | None | None | None | None | N |
| M/Y | 0.9246 | likely_pathogenic | 0.9177 | pathogenic | -0.738 | Destabilizing | 0.993 | D | 0.817 | 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.