Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15172 | 45739;45740;45741 | chr2:178621204;178621203;178621202 | chr2:179485931;179485930;179485929 |
| N2AB | 13531 | 40816;40817;40818 | chr2:178621204;178621203;178621202 | chr2:179485931;179485930;179485929 |
| N2A | 12604 | 38035;38036;38037 | chr2:178621204;178621203;178621202 | chr2:179485931;179485930;179485929 |
| N2B | 6107 | 18544;18545;18546 | chr2:178621204;178621203;178621202 | chr2:179485931;179485930;179485929 |
| Novex-1 | 6232 | 18919;18920;18921 | chr2:178621204;178621203;178621202 | chr2:179485931;179485930;179485929 |
| Novex-2 | 6299 | 19120;19121;19122 | chr2:178621204;178621203;178621202 | chr2:179485931;179485930;179485929 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs766651994  |
0.383 | 0.999 | N | 0.715 | 0.416 | 0.353336612579 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| K/E | rs766651994 |
0.383 | 0.999 | N | 0.715 | 0.416 | 0.353336612579 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| K/E | rs766651994 |
0.383 | 0.999 | N | 0.715 | 0.416 | 0.353336612579 | gnomAD-4.0.0 | 1.05432E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44162E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6969 | likely_pathogenic | 0.6403 | pathogenic | -0.572 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/C | 0.891 | likely_pathogenic | 0.852 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| K/D | 0.759 | likely_pathogenic | 0.6855 | pathogenic | 0.151 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| K/E | 0.3388 | likely_benign | 0.3084 | benign | 0.227 | Stabilizing | 0.999 | D | 0.715 | prob.delet. | N | 0.506430877 | None | None | N |
| K/F | 0.8841 | likely_pathogenic | 0.8694 | pathogenic | -0.485 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/G | 0.6474 | likely_pathogenic | 0.5992 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| K/H | 0.5106 | ambiguous | 0.4824 | ambiguous | -1.187 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| K/I | 0.6474 | likely_pathogenic | 0.6151 | pathogenic | 0.198 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.552162991 | None | None | N |
| K/L | 0.5307 | ambiguous | 0.4954 | ambiguous | 0.198 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| K/M | 0.3692 | ambiguous | 0.333 | benign | 0.122 | Stabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| K/N | 0.5058 | ambiguous | 0.432 | ambiguous | -0.25 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.509488873 | None | None | N |
| K/P | 0.8307 | likely_pathogenic | 0.8018 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| K/Q | 0.1989 | likely_benign | 0.1891 | benign | -0.442 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.506181568 | None | None | N |
| K/R | 0.1021 | likely_benign | 0.1047 | benign | -0.378 | Destabilizing | 0.999 | D | 0.634 | neutral | N | 0.50341418 | None | None | N |
| K/S | 0.6423 | likely_pathogenic | 0.5689 | pathogenic | -1.007 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| K/T | 0.3859 | ambiguous | 0.3322 | benign | -0.74 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.495392752 | None | None | N |
| K/V | 0.6425 | likely_pathogenic | 0.5978 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| K/W | 0.8699 | likely_pathogenic | 0.8596 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| K/Y | 0.7587 | likely_pathogenic | 0.7436 | pathogenic | 0.017 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | 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.