Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21191 | 63796;63797;63798 | chr2:178587738;178587737;178587736 | chr2:179452465;179452464;179452463 |
| N2AB | 19550 | 58873;58874;58875 | chr2:178587738;178587737;178587736 | chr2:179452465;179452464;179452463 |
| N2A | 18623 | 56092;56093;56094 | chr2:178587738;178587737;178587736 | chr2:179452465;179452464;179452463 |
| N2B | 12126 | 36601;36602;36603 | chr2:178587738;178587737;178587736 | chr2:179452465;179452464;179452463 |
| Novex-1 | 12251 | 36976;36977;36978 | chr2:178587738;178587737;178587736 | chr2:179452465;179452464;179452463 |
| Novex-2 | 12318 | 37177;37178;37179 | chr2:178587738;178587737;178587736 | chr2:179452465;179452464;179452463 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 1.0 | N | 0.706 | 0.366 | 0.324986149311 | gnomAD-4.0.0 | 3.42362E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.5996E-06 | 0 | 1.65793E-05 |
| P/R | rs1425522000  |
0.061 | 1.0 | N | 0.758 | 0.455 | 0.423597194605 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| P/R | rs1425522000 |
0.061 | 1.0 | N | 0.758 | 0.455 | 0.423597194605 | gnomAD-4.0.0 | 1.594E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86244E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2266 | likely_benign | 0.2158 | benign | -1.425 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.491302482 | None | None | I |
| P/C | 0.8691 | likely_pathogenic | 0.8663 | pathogenic | -0.947 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/D | 0.8958 | likely_pathogenic | 0.8903 | pathogenic | -1.269 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| P/E | 0.8251 | likely_pathogenic | 0.7942 | pathogenic | -1.307 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| P/F | 0.951 | likely_pathogenic | 0.944 | pathogenic | -1.218 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| P/G | 0.7367 | likely_pathogenic | 0.7355 | pathogenic | -1.705 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/H | 0.6915 | likely_pathogenic | 0.6777 | pathogenic | -1.203 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.471100571 | None | None | I |
| P/I | 0.845 | likely_pathogenic | 0.8337 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| P/K | 0.9115 | likely_pathogenic | 0.8944 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/L | 0.5648 | likely_pathogenic | 0.533 | ambiguous | -0.772 | Destabilizing | 1.0 | D | 0.76 | deleterious | N | 0.466972741 | None | None | I |
| P/M | 0.7876 | likely_pathogenic | 0.7811 | pathogenic | -0.52 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| P/N | 0.7939 | likely_pathogenic | 0.7957 | pathogenic | -0.928 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| P/Q | 0.6192 | likely_pathogenic | 0.5909 | pathogenic | -1.161 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| P/R | 0.8008 | likely_pathogenic | 0.7622 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.758 | deleterious | N | 0.505135784 | None | None | I |
| P/S | 0.3483 | ambiguous | 0.3308 | benign | -1.417 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.419207524 | None | None | I |
| P/T | 0.3284 | likely_benign | 0.3313 | benign | -1.351 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.39163692 | None | None | I |
| P/V | 0.6735 | likely_pathogenic | 0.6592 | pathogenic | -0.954 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| P/W | 0.9723 | likely_pathogenic | 0.9691 | pathogenic | -1.349 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| P/Y | 0.9348 | likely_pathogenic | 0.9306 | pathogenic | -1.089 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | 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.