Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17455 | 52588;52589;52590 | chr2:178608648;178608647;178608646 | chr2:179473375;179473374;179473373 |
| N2AB | 15814 | 47665;47666;47667 | chr2:178608648;178608647;178608646 | chr2:179473375;179473374;179473373 |
| N2A | 14887 | 44884;44885;44886 | chr2:178608648;178608647;178608646 | chr2:179473375;179473374;179473373 |
| N2B | 8390 | 25393;25394;25395 | chr2:178608648;178608647;178608646 | chr2:179473375;179473374;179473373 |
| Novex-1 | 8515 | 25768;25769;25770 | chr2:178608648;178608647;178608646 | chr2:179473375;179473374;179473373 |
| Novex-2 | 8582 | 25969;25970;25971 | chr2:178608648;178608647;178608646 | chr2:179473375;179473374;179473373 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs757257344  |
-1.357 | 0.37 | N | 0.413 | 0.201 | 0.272205846399 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | I | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/A | rs757257344 |
-1.357 | 0.37 | N | 0.413 | 0.201 | 0.272205846399 | gnomAD-4.0.0 | 1.59575E-06 | None | None | None | None | I | None | 0 | 2.29368E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs1489703004 |
-0.719 | 0.994 | N | 0.72 | 0.363 | 0.603927275247 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| P/L | rs1489703004 |
-0.719 | 0.994 | N | 0.72 | 0.363 | 0.603927275247 | gnomAD-4.0.0 | 4.11029E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47826E-04 | 3.60046E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0973 | likely_benign | 0.1011 | benign | -1.003 | Destabilizing | 0.37 | N | 0.413 | neutral | N | 0.484697089 | None | None | I |
| P/C | 0.5532 | ambiguous | 0.5483 | ambiguous | -0.661 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| P/D | 0.426 | ambiguous | 0.4599 | ambiguous | -0.826 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | I |
| P/E | 0.2423 | likely_benign | 0.255 | benign | -0.913 | Destabilizing | 0.983 | D | 0.663 | neutral | None | None | None | None | I |
| P/F | 0.4139 | ambiguous | 0.4319 | ambiguous | -0.988 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| P/G | 0.4016 | ambiguous | 0.419 | ambiguous | -1.208 | Destabilizing | 0.983 | D | 0.674 | neutral | None | None | None | None | I |
| P/H | 0.2428 | likely_benign | 0.249 | benign | -0.718 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| P/I | 0.2329 | likely_benign | 0.2347 | benign | -0.584 | Destabilizing | 0.998 | D | 0.777 | deleterious | None | None | None | None | I |
| P/K | 0.2743 | likely_benign | 0.2851 | benign | -0.876 | Destabilizing | 0.643 | D | 0.423 | neutral | None | None | None | None | I |
| P/L | 0.1039 | likely_benign | 0.1027 | benign | -0.584 | Destabilizing | 0.994 | D | 0.72 | prob.delet. | N | 0.504765717 | None | None | I |
| P/M | 0.2558 | likely_benign | 0.2541 | benign | -0.43 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| P/N | 0.3665 | ambiguous | 0.3713 | ambiguous | -0.519 | Destabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | I |
| P/Q | 0.172 | likely_benign | 0.1738 | benign | -0.795 | Destabilizing | 0.994 | D | 0.705 | prob.neutral | N | 0.490526983 | None | None | I |
| P/R | 0.2364 | likely_benign | 0.2463 | benign | -0.258 | Destabilizing | 0.987 | D | 0.718 | prob.delet. | N | 0.50524572 | None | None | I |
| P/S | 0.164 | likely_benign | 0.1674 | benign | -0.919 | Destabilizing | 0.956 | D | 0.659 | neutral | N | 0.521484608 | None | None | I |
| P/T | 0.1441 | likely_benign | 0.155 | benign | -0.911 | Destabilizing | 0.994 | D | 0.667 | neutral | D | 0.524447556 | None | None | I |
| P/V | 0.1729 | likely_benign | 0.1762 | benign | -0.688 | Destabilizing | 0.995 | D | 0.672 | neutral | None | None | None | None | I |
| P/W | 0.6852 | likely_pathogenic | 0.7017 | pathogenic | -1.066 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| P/Y | 0.4199 | ambiguous | 0.4406 | ambiguous | -0.808 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
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.