Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31335 | 94228;94229;94230 | chr2:178547623;178547622;178547621 | chr2:179412350;179412349;179412348 |
| N2AB | 29694 | 89305;89306;89307 | chr2:178547623;178547622;178547621 | chr2:179412350;179412349;179412348 |
| N2A | 28767 | 86524;86525;86526 | chr2:178547623;178547622;178547621 | chr2:179412350;179412349;179412348 |
| N2B | 22270 | 67033;67034;67035 | chr2:178547623;178547622;178547621 | chr2:179412350;179412349;179412348 |
| Novex-1 | 22395 | 67408;67409;67410 | chr2:178547623;178547622;178547621 | chr2:179412350;179412349;179412348 |
| Novex-2 | 22462 | 67609;67610;67611 | chr2:178547623;178547622;178547621 | chr2:179412350;179412349;179412348 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 1.0 | N | 0.727 | 0.482 | 0.487843537783 | gnomAD-4.0.0 | 1.36835E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31863E-05 | 0 |
| D/E | rs779852538  |
-0.103 | 1.0 | N | 0.391 | 0.239 | 0.422040124859 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/E | rs779852538 |
-0.103 | 1.0 | N | 0.391 | 0.239 | 0.422040124859 | gnomAD-4.0.0 | 6.84172E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99436E-07 | 0 | 0 |
| D/G | None | None | 1.0 | N | 0.681 | 0.527 | 0.418718287753 | gnomAD-4.0.0 | 6.84173E-07 | None | None | None | None | I | None | 2.98757E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | None | None | 1.0 | N | 0.637 | 0.43 | 0.437527004654 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6718 | likely_pathogenic | 0.5774 | pathogenic | -0.289 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.474127035 | None | None | I |
| D/C | 0.9021 | likely_pathogenic | 0.8758 | pathogenic | 0.121 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| D/E | 0.4435 | ambiguous | 0.3724 | ambiguous | -0.26 | Destabilizing | 1.0 | D | 0.391 | neutral | N | 0.512456907 | None | None | I |
| D/F | 0.8577 | likely_pathogenic | 0.8215 | pathogenic | -0.294 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| D/G | 0.5947 | likely_pathogenic | 0.5022 | ambiguous | -0.467 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.482369468 | None | None | I |
| D/H | 0.7987 | likely_pathogenic | 0.72 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.476773608 | None | None | I |
| D/I | 0.7994 | likely_pathogenic | 0.7252 | pathogenic | 0.128 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| D/K | 0.9096 | likely_pathogenic | 0.8616 | pathogenic | 0.431 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| D/L | 0.8322 | likely_pathogenic | 0.7758 | pathogenic | 0.128 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| D/M | 0.9246 | likely_pathogenic | 0.8841 | pathogenic | 0.303 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| D/N | 0.4038 | ambiguous | 0.3336 | benign | 0.13 | Stabilizing | 1.0 | D | 0.651 | neutral | N | 0.467188048 | None | None | I |
| D/P | 0.9716 | likely_pathogenic | 0.9634 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/Q | 0.8381 | likely_pathogenic | 0.7643 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| D/R | 0.8796 | likely_pathogenic | 0.8306 | pathogenic | 0.511 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| D/S | 0.5398 | ambiguous | 0.4363 | ambiguous | 0.045 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| D/T | 0.7147 | likely_pathogenic | 0.6107 | pathogenic | 0.189 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| D/V | 0.6084 | likely_pathogenic | 0.5323 | ambiguous | 0.01 | Stabilizing | 1.0 | D | 0.749 | deleterious | N | 0.493218795 | None | None | I |
| D/W | 0.9651 | likely_pathogenic | 0.9547 | pathogenic | -0.175 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/Y | 0.5385 | ambiguous | 0.4756 | ambiguous | -0.059 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.507224445 | 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.