Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31709 | 95350;95351;95352 | chr2:178546111;178546110;178546109 | chr2:179410838;179410837;179410836 |
| N2AB | 30068 | 90427;90428;90429 | chr2:178546111;178546110;178546109 | chr2:179410838;179410837;179410836 |
| N2A | 29141 | 87646;87647;87648 | chr2:178546111;178546110;178546109 | chr2:179410838;179410837;179410836 |
| N2B | 22644 | 68155;68156;68157 | chr2:178546111;178546110;178546109 | chr2:179410838;179410837;179410836 |
| Novex-1 | 22769 | 68530;68531;68532 | chr2:178546111;178546110;178546109 | chr2:179410838;179410837;179410836 |
| Novex-2 | 22836 | 68731;68732;68733 | chr2:178546111;178546110;178546109 | chr2:179410838;179410837;179410836 |
| 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/H | rs869320739  |
None | 0.999 | D | 0.744 | 0.603 | 0.530606565545 |
Palmio (2019)
| None |
HMERF 
|
het | None | None | N | Genetic analysis of genes in 12 HMERF families; co-segregates with condition (n = 1, 1 affected (total 2)) | None | None | None | None | None | None | None | None | None | None | None |
| P/R | rs869320739 |
-0.93 | 0.235 | D | 0.464 | 0.811 | 0.36256342048 |
Palmio (2013)
Hedberg (2014)
| None |
HMERF
|
het | None | None | N | WES/WGS prioritisation in 12 HMERF families; dominant effect, full penetrance (n = 3, 3 affected (total 6)) | None | None | None | None | None | None | None | None | None | None | None |
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 | 0.8199 | likely_pathogenic | 0.9041 | pathogenic | -1.515 | Destabilizing | 0.977 | D | 0.652 | neutral | D | 0.529542663 | None | None | N |
| P/C | 0.9859 | likely_pathogenic | 0.9938 | pathogenic | -1.819 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/D | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -2.758 | Highly Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| P/E | 0.998 | likely_pathogenic | 0.9989 | pathogenic | -2.735 | Highly Destabilizing | 0.995 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/F | 0.9992 | likely_pathogenic | 0.9996 | pathogenic | -1.293 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| P/G | 0.9923 | likely_pathogenic | 0.9959 | pathogenic | -1.813 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | N |
| P/H | 0.9968 | likely_pathogenic | 0.9984 | pathogenic | -1.198 | Destabilizing | 0.999 | D | 0.744 | deleterious | D | 0.560270671 | None | None | N |
| P/I | 0.9843 | likely_pathogenic | 0.9935 | pathogenic | -0.772 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| P/K | 0.9982 | likely_pathogenic | 0.999 | pathogenic | -1.353 | Destabilizing | 0.966 | D | 0.697 | prob.neutral | None | None | None | None | N |
| P/L | 0.9597 | likely_pathogenic | 0.9789 | pathogenic | -0.772 | Destabilizing | 0.993 | D | 0.707 | prob.neutral | D | 0.560270671 | None | None | N |
| P/M | 0.994 | likely_pathogenic | 0.9975 | pathogenic | -0.893 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| P/N | 0.9989 | likely_pathogenic | 0.9994 | pathogenic | -1.511 | Destabilizing | 0.995 | D | 0.736 | prob.delet. | None | None | None | None | N |
| P/Q | 0.9955 | likely_pathogenic | 0.9978 | pathogenic | -1.754 | Destabilizing | 0.995 | D | 0.755 | deleterious | None | None | None | None | N |
| P/R | 0.9921 | likely_pathogenic | 0.9952 | pathogenic | -0.808 | Destabilizing | 0.235 | N | 0.464 | neutral | D | 0.548153898 | None | None | N |
| P/S | 0.979 | likely_pathogenic | 0.9906 | pathogenic | -1.907 | Destabilizing | 0.993 | D | 0.713 | prob.delet. | D | 0.558496245 | None | None | N |
| P/T | 0.9687 | likely_pathogenic | 0.9865 | pathogenic | -1.782 | Destabilizing | 0.997 | D | 0.717 | prob.delet. | D | 0.548153897 | None | None | N |
| P/V | 0.947 | likely_pathogenic | 0.976 | pathogenic | -0.99 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| P/W | 0.9997 | likely_pathogenic | 0.9999 | pathogenic | -1.508 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| P/Y | 0.9994 | likely_pathogenic | 0.9997 | pathogenic | -1.165 | Destabilizing | 1.0 | D | 0.746 | 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.