Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27060 | 81403;81404;81405 | chr2:178564954;178564953;178564952 | chr2:179429681;179429680;179429679 |
| N2AB | 25419 | 76480;76481;76482 | chr2:178564954;178564953;178564952 | chr2:179429681;179429680;179429679 |
| N2A | 24492 | 73699;73700;73701 | chr2:178564954;178564953;178564952 | chr2:179429681;179429680;179429679 |
| N2B | 17995 | 54208;54209;54210 | chr2:178564954;178564953;178564952 | chr2:179429681;179429680;179429679 |
| Novex-1 | 18120 | 54583;54584;54585 | chr2:178564954;178564953;178564952 | chr2:179429681;179429680;179429679 |
| Novex-2 | 18187 | 54784;54785;54786 | chr2:178564954;178564953;178564952 | chr2:179429681;179429680;179429679 |
| 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/Y | rs372875889  |
0.305 | 0.989 | N | 0.831 | 0.253 | None | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 1.24121E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs372875889 |
0.305 | 0.989 | N | 0.831 | 0.253 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs372875889 |
0.305 | 0.989 | N | 0.831 | 0.253 | None | gnomAD-4.0.0 | 3.10168E-06 | None | None | None | None | N | None | 5.35103E-05 | 0 | None | 0 | 0 | None | 1.56426E-05 | 0 | 0 | 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 | 0.2021 | likely_benign | 0.1959 | benign | -0.47 | Destabilizing | 0.799 | D | 0.577 | neutral | N | 0.510910616 | None | None | N |
| D/C | 0.6227 | likely_pathogenic | 0.5865 | pathogenic | -0.212 | Destabilizing | 0.998 | D | 0.828 | deleterious | None | None | None | None | N |
| D/E | 0.1604 | likely_benign | 0.1337 | benign | -0.514 | Destabilizing | 0.799 | D | 0.576 | neutral | N | 0.417904455 | None | None | N |
| D/F | 0.5752 | likely_pathogenic | 0.5355 | ambiguous | 0.212 | Stabilizing | 0.974 | D | 0.836 | deleterious | None | None | None | None | N |
| D/G | 0.3196 | likely_benign | 0.313 | benign | -0.859 | Destabilizing | 0.666 | D | 0.612 | neutral | D | 0.522031687 | None | None | N |
| D/H | 0.4158 | ambiguous | 0.3818 | ambiguous | -0.014 | Destabilizing | 0.991 | D | 0.688 | prob.delet. | N | 0.481805216 | None | None | N |
| D/I | 0.2642 | likely_benign | 0.2293 | benign | 0.569 | Stabilizing | 0.903 | D | 0.628 | neutral | None | None | None | None | N |
| D/K | 0.5693 | likely_pathogenic | 0.5487 | ambiguous | -0.291 | Destabilizing | 0.949 | D | 0.646 | neutral | None | None | None | None | N |
| D/L | 0.3079 | likely_benign | 0.2829 | benign | 0.569 | Stabilizing | 0.725 | D | 0.639 | neutral | None | None | None | None | N |
| D/M | 0.559 | ambiguous | 0.5021 | ambiguous | 0.938 | Stabilizing | 0.993 | D | 0.796 | deleterious | None | None | None | None | N |
| D/N | 0.148 | likely_benign | 0.1236 | benign | -0.885 | Destabilizing | 0.028 | N | 0.303 | neutral | N | 0.500925696 | None | None | N |
| D/P | 0.6053 | likely_pathogenic | 0.6394 | pathogenic | 0.248 | Stabilizing | 0.991 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/Q | 0.427 | ambiguous | 0.3877 | ambiguous | -0.695 | Destabilizing | 0.974 | D | 0.631 | neutral | None | None | None | None | N |
| D/R | 0.6286 | likely_pathogenic | 0.6142 | pathogenic | -0.045 | Destabilizing | 0.949 | D | 0.837 | deleterious | None | None | None | None | N |
| D/S | 0.179 | likely_benign | 0.1604 | benign | -1.155 | Destabilizing | 0.725 | D | 0.585 | neutral | None | None | None | None | N |
| D/T | 0.2316 | likely_benign | 0.2027 | benign | -0.824 | Destabilizing | 0.841 | D | 0.673 | prob.neutral | None | None | None | None | N |
| D/V | 0.1589 | likely_benign | 0.1424 | benign | 0.248 | Stabilizing | 0.051 | N | 0.495 | neutral | N | 0.462580739 | None | None | N |
| D/W | 0.9076 | likely_pathogenic | 0.905 | pathogenic | 0.456 | Stabilizing | 0.998 | D | 0.772 | deleterious | None | None | None | None | N |
| D/Y | 0.2784 | likely_benign | 0.2568 | benign | 0.482 | Stabilizing | 0.989 | D | 0.831 | deleterious | N | 0.511176871 | 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.