Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14453 | 43582;43583;43584 | chr2:178632649;178632648;178632647 | chr2:179497376;179497375;179497374 |
| N2AB | 12812 | 38659;38660;38661 | chr2:178632649;178632648;178632647 | chr2:179497376;179497375;179497374 |
| N2A | 11885 | 35878;35879;35880 | chr2:178632649;178632648;178632647 | chr2:179497376;179497375;179497374 |
| N2B | 5388 | 16387;16388;16389 | chr2:178632649;178632648;178632647 | chr2:179497376;179497375;179497374 |
| Novex-1 | 5513 | 16762;16763;16764 | chr2:178632649;178632648;178632647 | chr2:179497376;179497375;179497374 |
| Novex-2 | 5580 | 16963;16964;16965 | chr2:178632649;178632648;178632647 | chr2:179497376;179497375;179497374 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs777429220  |
-2.057 | 0.612 | D | 0.614 | 0.326 | 0.422283790207 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| F/C | rs777429220 |
-2.057 | 0.612 | D | 0.614 | 0.326 | 0.422283790207 | gnomAD-4.0.0 | 3.18369E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86574E-05 | 0 |
| F/L | rs878966051 |
None | None | N | 0.188 | 0.193 | 0.37262878642 | gnomAD-4.0.0 | 1.59184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85964E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.2833 | likely_benign | 0.2538 | benign | -2.903 | Highly Destabilizing | 0.016 | N | 0.557 | neutral | None | None | None | None | N |
| F/C | 0.1901 | likely_benign | 0.1701 | benign | -1.948 | Destabilizing | 0.612 | D | 0.614 | neutral | D | 0.559805697 | None | None | N |
| F/D | 0.6607 | likely_pathogenic | 0.621 | pathogenic | -2.827 | Highly Destabilizing | 0.214 | N | 0.684 | prob.neutral | None | None | None | None | N |
| F/E | 0.6268 | likely_pathogenic | 0.583 | pathogenic | -2.658 | Highly Destabilizing | 0.072 | N | 0.671 | neutral | None | None | None | None | N |
| F/G | 0.5654 | likely_pathogenic | 0.5097 | ambiguous | -3.334 | Highly Destabilizing | 0.072 | N | 0.661 | neutral | None | None | None | None | N |
| F/H | 0.3803 | ambiguous | 0.3698 | ambiguous | -1.754 | Destabilizing | 0.001 | N | 0.457 | neutral | None | None | None | None | N |
| F/I | 0.0558 | likely_benign | 0.0557 | benign | -1.521 | Destabilizing | None | N | 0.38 | neutral | N | 0.499072437 | None | None | N |
| F/K | 0.5476 | ambiguous | 0.506 | ambiguous | -2.054 | Highly Destabilizing | 0.072 | N | 0.694 | prob.neutral | None | None | None | None | N |
| F/L | 0.371 | ambiguous | 0.3787 | ambiguous | -1.521 | Destabilizing | None | N | 0.188 | neutral | N | 0.509085224 | None | None | N |
| F/M | 0.1611 | likely_benign | 0.1601 | benign | -1.221 | Destabilizing | 0.214 | N | 0.634 | neutral | None | None | None | None | N |
| F/N | 0.3342 | likely_benign | 0.3225 | benign | -2.371 | Highly Destabilizing | 0.214 | N | 0.679 | prob.neutral | None | None | None | None | N |
| F/P | 0.8956 | likely_pathogenic | 0.8673 | pathogenic | -1.989 | Destabilizing | 0.356 | N | 0.679 | prob.neutral | None | None | None | None | N |
| F/Q | 0.5228 | ambiguous | 0.4852 | ambiguous | -2.391 | Highly Destabilizing | 0.214 | N | 0.683 | prob.neutral | None | None | None | None | N |
| F/R | 0.4211 | ambiguous | 0.3872 | ambiguous | -1.426 | Destabilizing | 0.214 | N | 0.667 | neutral | None | None | None | None | N |
| F/S | 0.2602 | likely_benign | 0.2423 | benign | -3.112 | Highly Destabilizing | 0.029 | N | 0.615 | neutral | D | 0.584377734 | None | None | N |
| F/T | 0.155 | likely_benign | 0.1511 | benign | -2.831 | Highly Destabilizing | None | N | 0.511 | neutral | None | None | None | None | N |
| F/V | 0.0793 | likely_benign | 0.0743 | benign | -1.989 | Destabilizing | None | N | 0.361 | neutral | N | 0.500231471 | None | None | N |
| F/W | 0.3214 | likely_benign | 0.2971 | benign | -0.63 | Destabilizing | 0.864 | D | 0.601 | neutral | None | None | None | None | N |
| F/Y | 0.1569 | likely_benign | 0.1441 | benign | -0.967 | Destabilizing | 0.001 | N | 0.336 | neutral | N | 0.442552334 | 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.