Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31316 | 94171;94172;94173 | chr2:178547680;178547679;178547678 | chr2:179412407;179412406;179412405 |
| N2AB | 29675 | 89248;89249;89250 | chr2:178547680;178547679;178547678 | chr2:179412407;179412406;179412405 |
| N2A | 28748 | 86467;86468;86469 | chr2:178547680;178547679;178547678 | chr2:179412407;179412406;179412405 |
| N2B | 22251 | 66976;66977;66978 | chr2:178547680;178547679;178547678 | chr2:179412407;179412406;179412405 |
| Novex-1 | 22376 | 67351;67352;67353 | chr2:178547680;178547679;178547678 | chr2:179412407;179412406;179412405 |
| Novex-2 | 22443 | 67552;67553;67554 | chr2:178547680;178547679;178547678 | chr2:179412407;179412406;179412405 |
| 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 | rs79459914  |
-2.125 | 0.896 | N | 0.697 | 0.359 | 0.551009825273 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/T | rs79459914 |
-2.125 | 0.896 | N | 0.697 | 0.359 | 0.551009825273 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs79459914 |
-2.125 | 0.896 | N | 0.697 | 0.359 | 0.551009825273 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs79459914 |
-2.125 | 0.896 | N | 0.697 | 0.359 | 0.551009825273 | gnomAD-4.0.0 | 5.57647E-06 | None | None | None | None | N | None | 1.33252E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78066E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6826 | likely_pathogenic | 0.6006 | pathogenic | -2.215 | Highly Destabilizing | 0.702 | D | 0.659 | neutral | None | None | None | None | N |
| I/C | 0.9217 | likely_pathogenic | 0.9016 | pathogenic | -1.645 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/D | 0.9953 | likely_pathogenic | 0.9934 | pathogenic | -2.111 | Highly Destabilizing | 0.996 | D | 0.801 | deleterious | None | None | None | None | N |
| I/E | 0.9866 | likely_pathogenic | 0.9821 | pathogenic | -1.893 | Destabilizing | 0.988 | D | 0.786 | deleterious | None | None | None | None | N |
| I/F | 0.4534 | ambiguous | 0.4566 | ambiguous | -1.211 | Destabilizing | 0.984 | D | 0.685 | prob.neutral | N | 0.504242855 | None | None | N |
| I/G | 0.9728 | likely_pathogenic | 0.9616 | pathogenic | -2.76 | Highly Destabilizing | 0.988 | D | 0.766 | deleterious | None | None | None | None | N |
| I/H | 0.989 | likely_pathogenic | 0.9856 | pathogenic | -2.239 | Highly Destabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| I/K | 0.977 | likely_pathogenic | 0.9729 | pathogenic | -1.572 | Destabilizing | 0.988 | D | 0.787 | deleterious | None | None | None | None | N |
| I/L | 0.1417 | likely_benign | 0.1271 | benign | -0.657 | Destabilizing | 0.437 | N | 0.455 | neutral | N | 0.41164962 | None | None | N |
| I/M | 0.1696 | likely_benign | 0.1569 | benign | -0.77 | Destabilizing | 0.984 | D | 0.666 | neutral | N | 0.504936288 | None | None | N |
| I/N | 0.9612 | likely_pathogenic | 0.9489 | pathogenic | -1.831 | Destabilizing | 0.995 | D | 0.813 | deleterious | N | 0.484499517 | None | None | N |
| I/P | 0.9028 | likely_pathogenic | 0.8672 | pathogenic | -1.154 | Destabilizing | 0.996 | D | 0.803 | deleterious | None | None | None | None | N |
| I/Q | 0.9765 | likely_pathogenic | 0.9714 | pathogenic | -1.678 | Destabilizing | 0.996 | D | 0.813 | deleterious | None | None | None | None | N |
| I/R | 0.9655 | likely_pathogenic | 0.9609 | pathogenic | -1.412 | Destabilizing | 0.996 | D | 0.815 | deleterious | None | None | None | None | N |
| I/S | 0.9071 | likely_pathogenic | 0.8764 | pathogenic | -2.59 | Highly Destabilizing | 0.984 | D | 0.75 | deleterious | N | 0.495766917 | None | None | N |
| I/T | 0.6591 | likely_pathogenic | 0.585 | pathogenic | -2.218 | Highly Destabilizing | 0.896 | D | 0.697 | prob.neutral | N | 0.469015381 | None | None | N |
| I/V | 0.0695 | likely_benign | 0.0662 | benign | -1.154 | Destabilizing | 0.004 | N | 0.213 | neutral | N | 0.403113069 | None | None | N |
| I/W | 0.977 | likely_pathogenic | 0.9737 | pathogenic | -1.541 | Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| I/Y | 0.9464 | likely_pathogenic | 0.9367 | pathogenic | -1.231 | Destabilizing | 0.996 | D | 0.745 | 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.