Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24272 | 73039;73040;73041 | chr2:178573318;178573317;178573316 | chr2:179438045;179438044;179438043 |
| N2AB | 22631 | 68116;68117;68118 | chr2:178573318;178573317;178573316 | chr2:179438045;179438044;179438043 |
| N2A | 21704 | 65335;65336;65337 | chr2:178573318;178573317;178573316 | chr2:179438045;179438044;179438043 |
| N2B | 15207 | 45844;45845;45846 | chr2:178573318;178573317;178573316 | chr2:179438045;179438044;179438043 |
| Novex-1 | 15332 | 46219;46220;46221 | chr2:178573318;178573317;178573316 | chr2:179438045;179438044;179438043 |
| Novex-2 | 15399 | 46420;46421;46422 | chr2:178573318;178573317;178573316 | chr2:179438045;179438044;179438043 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | None | None | 0.942 | N | 0.724 | 0.36 | 0.682271003597 | gnomAD-4.0.0 | 1.71883E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.64322E-05 | 0 |
| C/G | rs1559424305  |
None | 0.97 | N | 0.681 | 0.521 | 0.744267717487 | gnomAD-2.1.1 | 4.75E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.93E-05 | None | 0 | None | 0 | 0 | 0 |
| C/G | rs1559424305 |
None | 0.97 | N | 0.681 | 0.521 | 0.744267717487 | gnomAD-4.0.0 | 1.71687E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.81057E-05 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs377121903 |
-1.285 | 0.97 | N | 0.741 | 0.419 | None | gnomAD-2.1.1 | 4.77E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.02E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7013 | likely_pathogenic | 0.6562 | pathogenic | -1.984 | Destabilizing | 0.559 | D | 0.415 | neutral | None | None | None | None | N |
| C/D | 0.9921 | likely_pathogenic | 0.9939 | pathogenic | -0.827 | Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | None | N |
| C/E | 0.9946 | likely_pathogenic | 0.9957 | pathogenic | -0.673 | Destabilizing | 0.978 | D | 0.765 | deleterious | None | None | None | None | N |
| C/F | 0.7642 | likely_pathogenic | 0.8367 | pathogenic | -1.197 | Destabilizing | 0.942 | D | 0.724 | prob.delet. | N | 0.482201203 | None | None | N |
| C/G | 0.6252 | likely_pathogenic | 0.585 | pathogenic | -2.327 | Highly Destabilizing | 0.97 | D | 0.681 | prob.neutral | N | 0.509588303 | None | None | N |
| C/H | 0.949 | likely_pathogenic | 0.9785 | pathogenic | -2.241 | Highly Destabilizing | 0.998 | D | 0.764 | deleterious | None | None | None | None | N |
| C/I | 0.7556 | likely_pathogenic | 0.7381 | pathogenic | -1.074 | Destabilizing | 0.754 | D | 0.471 | neutral | None | None | None | None | N |
| C/K | 0.9969 | likely_pathogenic | 0.9976 | pathogenic | -1.359 | Destabilizing | 0.978 | D | 0.734 | prob.delet. | None | None | None | None | N |
| C/L | 0.8422 | likely_pathogenic | 0.8339 | pathogenic | -1.074 | Destabilizing | 0.559 | D | 0.471 | neutral | None | None | None | None | N |
| C/M | 0.9034 | likely_pathogenic | 0.9086 | pathogenic | 0.129 | Stabilizing | 0.978 | D | 0.682 | prob.neutral | None | None | None | None | N |
| C/N | 0.9296 | likely_pathogenic | 0.9493 | pathogenic | -1.541 | Destabilizing | 0.993 | D | 0.78 | deleterious | None | None | None | None | N |
| C/P | 0.9931 | likely_pathogenic | 0.9905 | pathogenic | -1.353 | Destabilizing | 0.993 | D | 0.774 | deleterious | None | None | None | None | N |
| C/Q | 0.977 | likely_pathogenic | 0.9845 | pathogenic | -1.311 | Destabilizing | 0.993 | D | 0.775 | deleterious | None | None | None | None | N |
| C/R | 0.9777 | likely_pathogenic | 0.9814 | pathogenic | -1.292 | Destabilizing | 0.97 | D | 0.781 | deleterious | N | 0.519170182 | None | None | N |
| C/S | 0.6915 | likely_pathogenic | 0.6887 | pathogenic | -2.06 | Highly Destabilizing | 0.904 | D | 0.578 | neutral | N | 0.477797111 | None | None | N |
| C/T | 0.8036 | likely_pathogenic | 0.795 | pathogenic | -1.718 | Destabilizing | 0.86 | D | 0.533 | neutral | None | None | None | None | N |
| C/V | 0.5644 | likely_pathogenic | 0.5388 | ambiguous | -1.353 | Destabilizing | 0.019 | N | 0.371 | neutral | None | None | None | None | N |
| C/W | 0.9425 | likely_pathogenic | 0.9682 | pathogenic | -1.27 | Destabilizing | 0.997 | D | 0.729 | prob.delet. | N | 0.521958567 | None | None | N |
| C/Y | 0.8583 | likely_pathogenic | 0.9132 | pathogenic | -1.268 | Destabilizing | 0.97 | D | 0.741 | deleterious | N | 0.509081324 | 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.