Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19827 | 59704;59705;59706 | chr2:178592526;178592525;178592524 | chr2:179457253;179457252;179457251 |
| N2AB | 18186 | 54781;54782;54783 | chr2:178592526;178592525;178592524 | chr2:179457253;179457252;179457251 |
| N2A | 17259 | 52000;52001;52002 | chr2:178592526;178592525;178592524 | chr2:179457253;179457252;179457251 |
| N2B | 10762 | 32509;32510;32511 | chr2:178592526;178592525;178592524 | chr2:179457253;179457252;179457251 |
| Novex-1 | 10887 | 32884;32885;32886 | chr2:178592526;178592525;178592524 | chr2:179457253;179457252;179457251 |
| Novex-2 | 10954 | 33085;33086;33087 | chr2:178592526;178592525;178592524 | chr2:179457253;179457252;179457251 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.912 | N | 0.68 | 0.362 | 0.440810947182 | gnomAD-4.0.0 | 1.59184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41313E-04 | 0 | 0 | 0 |
| A/T | rs1486455831  |
-1.454 | 0.324 | N | 0.557 | 0.175 | 0.287603790349 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.55308E-04 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs1486455831 |
-1.454 | 0.324 | N | 0.557 | 0.175 | 0.287603790349 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs1486455831 |
-1.454 | 0.324 | N | 0.557 | 0.175 | 0.287603790349 | gnomAD-4.0.0 | 6.57791E-06 | None | None | None | None | N | None | 0 | 6.55738E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | None | None | None | N | 0.169 | 0.151 | 0.163833314356 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3783 | ambiguous | 0.3426 | ambiguous | -0.941 | Destabilizing | 0.944 | D | 0.603 | neutral | None | None | None | None | N |
| A/D | 0.6204 | likely_pathogenic | 0.6377 | pathogenic | -1.015 | Destabilizing | 0.773 | D | 0.662 | neutral | N | 0.458561785 | None | None | N |
| A/E | 0.532 | ambiguous | 0.5684 | pathogenic | -0.977 | Destabilizing | 0.563 | D | 0.624 | neutral | None | None | None | None | N |
| A/F | 0.315 | likely_benign | 0.3153 | benign | -0.833 | Destabilizing | 0.69 | D | 0.669 | neutral | None | None | None | None | N |
| A/G | 0.2162 | likely_benign | 0.2279 | benign | -1.192 | Destabilizing | 0.492 | N | 0.558 | neutral | N | 0.476974188 | None | None | N |
| A/H | 0.6899 | likely_pathogenic | 0.7073 | pathogenic | -1.407 | Destabilizing | 0.981 | D | 0.617 | neutral | None | None | None | None | N |
| A/I | 0.1044 | likely_benign | 0.0968 | benign | -0.082 | Destabilizing | 0.043 | N | 0.535 | neutral | None | None | None | None | N |
| A/K | 0.7556 | likely_pathogenic | 0.7743 | pathogenic | -1.159 | Destabilizing | 0.563 | D | 0.627 | neutral | None | None | None | None | N |
| A/L | 0.1083 | likely_benign | 0.1124 | benign | -0.082 | Destabilizing | 0.116 | N | 0.517 | neutral | None | None | None | None | N |
| A/M | 0.1722 | likely_benign | 0.1666 | benign | -0.2 | Destabilizing | 0.69 | D | 0.669 | neutral | None | None | None | None | N |
| A/N | 0.4708 | ambiguous | 0.4717 | ambiguous | -0.977 | Destabilizing | 0.932 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/P | 0.1393 | likely_benign | 0.1465 | benign | -0.297 | Destabilizing | 0.912 | D | 0.68 | prob.neutral | N | 0.443304331 | None | None | N |
| A/Q | 0.6071 | likely_pathogenic | 0.6392 | pathogenic | -0.989 | Destabilizing | 0.932 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/R | 0.6888 | likely_pathogenic | 0.7272 | pathogenic | -0.998 | Destabilizing | 0.818 | D | 0.691 | prob.neutral | None | None | None | None | N |
| A/S | 0.1522 | likely_benign | 0.1508 | benign | -1.394 | Destabilizing | 0.324 | N | 0.553 | neutral | N | 0.433530055 | None | None | N |
| A/T | 0.0945 | likely_benign | 0.0892 | benign | -1.229 | Destabilizing | 0.324 | N | 0.557 | neutral | N | 0.445533773 | None | None | N |
| A/V | 0.0613 | likely_benign | 0.0588 | benign | -0.297 | Destabilizing | None | N | 0.169 | neutral | N | 0.326783805 | None | None | N |
| A/W | 0.8094 | likely_pathogenic | 0.8221 | pathogenic | -1.259 | Destabilizing | 0.981 | D | 0.701 | prob.neutral | None | None | None | None | N |
| A/Y | 0.5609 | ambiguous | 0.5501 | ambiguous | -0.794 | Destabilizing | 0.818 | D | 0.691 | prob.neutral | 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.