Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18142 | 54649;54650;54651 | chr2:178604263;178604262;178604261 | chr2:179468990;179468989;179468988 |
| N2AB | 16501 | 49726;49727;49728 | chr2:178604263;178604262;178604261 | chr2:179468990;179468989;179468988 |
| N2A | 15574 | 46945;46946;46947 | chr2:178604263;178604262;178604261 | chr2:179468990;179468989;179468988 |
| N2B | 9077 | 27454;27455;27456 | chr2:178604263;178604262;178604261 | chr2:179468990;179468989;179468988 |
| Novex-1 | 9202 | 27829;27830;27831 | chr2:178604263;178604262;178604261 | chr2:179468990;179468989;179468988 |
| Novex-2 | 9269 | 28030;28031;28032 | chr2:178604263;178604262;178604261 | chr2:179468990;179468989;179468988 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs1455326648  |
None | 0.961 | N | 0.622 | 0.324 | 0.210429274316 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/S | rs1455326648 |
None | 0.961 | N | 0.622 | 0.324 | 0.210429274316 | gnomAD-4.0.0 | 1.72692E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.09228E-06 | 0 | 0 |
| R/W | None | None | 1.0 | N | 0.677 | 0.458 | 0.424430313326 | gnomAD-4.0.0 | 1.72857E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.24359E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7335 | likely_pathogenic | 0.5702 | pathogenic | -1.476 | Destabilizing | 0.97 | D | 0.637 | neutral | None | None | None | None | N |
| R/C | 0.2741 | likely_benign | 0.1774 | benign | -1.671 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/D | 0.972 | likely_pathogenic | 0.9447 | pathogenic | -0.907 | Destabilizing | 0.996 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/E | 0.7675 | likely_pathogenic | 0.6605 | pathogenic | -0.729 | Destabilizing | 0.97 | D | 0.657 | neutral | None | None | None | None | N |
| R/F | 0.818 | likely_pathogenic | 0.6935 | pathogenic | -0.931 | Destabilizing | 0.999 | D | 0.756 | deleterious | None | None | None | None | N |
| R/G | 0.684 | likely_pathogenic | 0.5216 | ambiguous | -1.801 | Destabilizing | 0.98 | D | 0.672 | neutral | N | 0.472004349 | None | None | N |
| R/H | 0.2254 | likely_benign | 0.1624 | benign | -1.832 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/I | 0.6781 | likely_pathogenic | 0.5025 | ambiguous | -0.563 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| R/K | 0.1579 | likely_benign | 0.1266 | benign | -1.489 | Destabilizing | 0.122 | N | 0.335 | neutral | N | 0.409081823 | None | None | N |
| R/L | 0.5705 | likely_pathogenic | 0.4499 | ambiguous | -0.563 | Destabilizing | 0.985 | D | 0.672 | neutral | None | None | None | None | N |
| R/M | 0.5318 | ambiguous | 0.3673 | ambiguous | -1.036 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.461974945 | None | None | N |
| R/N | 0.9075 | likely_pathogenic | 0.8297 | pathogenic | -1.282 | Destabilizing | 0.996 | D | 0.665 | neutral | None | None | None | None | N |
| R/P | 0.9971 | likely_pathogenic | 0.9941 | pathogenic | -0.852 | Destabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | None | N |
| R/Q | 0.1759 | likely_benign | 0.1291 | benign | -1.179 | Destabilizing | 0.991 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/S | 0.784 | likely_pathogenic | 0.6262 | pathogenic | -2.006 | Highly Destabilizing | 0.961 | D | 0.622 | neutral | N | 0.44548534 | None | None | N |
| R/T | 0.5993 | likely_pathogenic | 0.4365 | ambiguous | -1.636 | Destabilizing | 0.98 | D | 0.635 | neutral | N | 0.455123544 | None | None | N |
| R/V | 0.7097 | likely_pathogenic | 0.5562 | ambiguous | -0.852 | Destabilizing | 0.996 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/W | 0.4871 | ambiguous | 0.3529 | ambiguous | -0.592 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.472511328 | None | None | N |
| R/Y | 0.6969 | likely_pathogenic | 0.5618 | ambiguous | -0.335 | Destabilizing | 0.999 | D | 0.745 | deleterious | 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.