Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27936 | 84031;84032;84033 | chr2:178562326;178562325;178562324 | chr2:179427053;179427052;179427051 |
| N2AB | 26295 | 79108;79109;79110 | chr2:178562326;178562325;178562324 | chr2:179427053;179427052;179427051 |
| N2A | 25368 | 76327;76328;76329 | chr2:178562326;178562325;178562324 | chr2:179427053;179427052;179427051 |
| N2B | 18871 | 56836;56837;56838 | chr2:178562326;178562325;178562324 | chr2:179427053;179427052;179427051 |
| Novex-1 | 18996 | 57211;57212;57213 | chr2:178562326;178562325;178562324 | chr2:179427053;179427052;179427051 |
| Novex-2 | 19063 | 57412;57413;57414 | chr2:178562326;178562325;178562324 | chr2:179427053;179427052;179427051 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs774435769  |
-2.854 | 0.998 | D | 0.686 | 0.757 | 0.797850590631 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.3113E-04 | None | 0 | 0 | 0 |
| V/A | rs774435769 |
-2.854 | 0.998 | D | 0.686 | 0.757 | 0.797850590631 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14422E-04 | 0 |
| V/A | rs774435769 |
-2.854 | 0.998 | D | 0.686 | 0.757 | 0.797850590631 | gnomAD-4.0.0 | 1.66807E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.74938E-04 | 0 |
| V/I | rs1703970661 |
None | 0.729 | N | 0.339 | 0.274 | 0.65404562455 | gnomAD-4.0.0 | 5.47831E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19804E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8168 | likely_pathogenic | 0.8687 | pathogenic | -2.513 | Highly Destabilizing | 0.998 | D | 0.686 | prob.neutral | D | 0.561696153 | None | None | N |
| V/C | 0.9773 | likely_pathogenic | 0.9826 | pathogenic | -1.899 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| V/D | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -3.435 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| V/E | 0.9958 | likely_pathogenic | 0.9961 | pathogenic | -3.137 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | D | 0.646431685 | None | None | N |
| V/F | 0.9321 | likely_pathogenic | 0.9486 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/G | 0.9527 | likely_pathogenic | 0.965 | pathogenic | -3.068 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.646431685 | None | None | N |
| V/H | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -2.882 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| V/I | 0.1063 | likely_benign | 0.1063 | benign | -0.885 | Destabilizing | 0.729 | D | 0.339 | neutral | N | 0.521269257 | None | None | N |
| V/K | 0.9979 | likely_pathogenic | 0.9978 | pathogenic | -2.042 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| V/L | 0.7706 | likely_pathogenic | 0.803 | pathogenic | -0.885 | Destabilizing | 0.942 | D | 0.63 | neutral | N | 0.520773474 | None | None | N |
| V/M | 0.8203 | likely_pathogenic | 0.8547 | pathogenic | -1.169 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| V/N | 0.9962 | likely_pathogenic | 0.9966 | pathogenic | -2.664 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| V/P | 0.9959 | likely_pathogenic | 0.9965 | pathogenic | -1.413 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| V/Q | 0.9962 | likely_pathogenic | 0.9968 | pathogenic | -2.338 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| V/R | 0.995 | likely_pathogenic | 0.9952 | pathogenic | -2.048 | Highly Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| V/S | 0.9729 | likely_pathogenic | 0.9791 | pathogenic | -3.13 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| V/T | 0.8875 | likely_pathogenic | 0.9109 | pathogenic | -2.696 | Highly Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/W | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.925 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/Y | 0.9957 | likely_pathogenic | 0.9964 | pathogenic | -1.673 | Destabilizing | 1.0 | D | 0.844 | 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.