Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18996 | 57211;57212;57213 | chr2:178598631;178598630;178598629 | chr2:179463358;179463357;179463356 |
| N2AB | 17355 | 52288;52289;52290 | chr2:178598631;178598630;178598629 | chr2:179463358;179463357;179463356 |
| N2A | 16428 | 49507;49508;49509 | chr2:178598631;178598630;178598629 | chr2:179463358;179463357;179463356 |
| N2B | 9931 | 30016;30017;30018 | chr2:178598631;178598630;178598629 | chr2:179463358;179463357;179463356 |
| Novex-1 | 10056 | 30391;30392;30393 | chr2:178598631;178598630;178598629 | chr2:179463358;179463357;179463356 |
| Novex-2 | 10123 | 30592;30593;30594 | chr2:178598631;178598630;178598629 | chr2:179463358;179463357;179463356 |
| 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/Q | rs541709149  |
-0.061 | 0.284 | N | 0.271 | 0.095 | 0.162503812791 | gnomAD-2.1.1 | 2.1E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.80297E-04 | None | 0 | 0 | 0 |
| K/Q | rs541709149 |
-0.061 | 0.284 | N | 0.271 | 0.095 | 0.162503812791 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| K/Q | rs541709149 |
-0.061 | 0.284 | N | 0.271 | 0.095 | 0.162503812791 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| K/Q | rs541709149 |
-0.061 | 0.284 | N | 0.271 | 0.095 | 0.162503812791 | gnomAD-4.0.0 | 8.72732E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.47119E-04 | 1.61103E-05 |
| K/R | rs1002471047 |
None | 0.865 | N | 0.484 | 0.176 | 0.271763555656 | gnomAD-4.0.0 | 9.6924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.72604E-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 | 0.4543 | ambiguous | 0.4907 | ambiguous | -0.393 | Destabilizing | 0.895 | D | 0.609 | neutral | None | None | None | None | N |
| K/C | 0.6911 | likely_pathogenic | 0.7092 | pathogenic | -0.539 | Destabilizing | 0.999 | D | 0.806 | deleterious | None | None | None | None | N |
| K/D | 0.8217 | likely_pathogenic | 0.8297 | pathogenic | -0.102 | Destabilizing | 0.983 | D | 0.762 | deleterious | None | None | None | None | N |
| K/E | 0.3045 | likely_benign | 0.3063 | benign | 0.012 | Stabilizing | 0.865 | D | 0.485 | neutral | N | 0.40562023 | None | None | N |
| K/F | 0.798 | likely_pathogenic | 0.8136 | pathogenic | -0.033 | Destabilizing | 0.999 | D | 0.804 | deleterious | None | None | None | None | N |
| K/G | 0.6924 | likely_pathogenic | 0.7166 | pathogenic | -0.756 | Destabilizing | 0.983 | D | 0.725 | prob.delet. | None | None | None | None | N |
| K/H | 0.3057 | likely_benign | 0.3095 | benign | -1.03 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| K/I | 0.3892 | ambiguous | 0.3917 | ambiguous | 0.54 | Stabilizing | 0.989 | D | 0.824 | deleterious | N | 0.502013413 | None | None | N |
| K/L | 0.4668 | ambiguous | 0.4884 | ambiguous | 0.54 | Stabilizing | 0.983 | D | 0.725 | prob.delet. | None | None | None | None | N |
| K/M | 0.3298 | likely_benign | 0.3233 | benign | 0.215 | Stabilizing | 0.998 | D | 0.762 | deleterious | None | None | None | None | N |
| K/N | 0.6131 | likely_pathogenic | 0.6575 | pathogenic | -0.478 | Destabilizing | 0.978 | D | 0.67 | neutral | N | 0.514057204 | None | None | N |
| K/P | 0.9798 | likely_pathogenic | 0.9842 | pathogenic | 0.26 | Stabilizing | 0.992 | D | 0.811 | deleterious | None | None | None | None | N |
| K/Q | 0.1665 | likely_benign | 0.1803 | benign | -0.479 | Destabilizing | 0.284 | N | 0.271 | neutral | N | 0.480077916 | None | None | N |
| K/R | 0.0788 | likely_benign | 0.0795 | benign | -0.616 | Destabilizing | 0.865 | D | 0.484 | neutral | N | 0.463743027 | None | None | N |
| K/S | 0.5495 | ambiguous | 0.5939 | pathogenic | -1.047 | Destabilizing | 0.895 | D | 0.552 | neutral | None | None | None | None | N |
| K/T | 0.236 | likely_benign | 0.2511 | benign | -0.73 | Destabilizing | 0.978 | D | 0.763 | deleterious | N | 0.45695034 | None | None | N |
| K/V | 0.3059 | likely_benign | 0.3177 | benign | 0.26 | Stabilizing | 0.983 | D | 0.783 | deleterious | None | None | None | None | N |
| K/W | 0.8251 | likely_pathogenic | 0.8244 | pathogenic | 0.029 | Stabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | N |
| K/Y | 0.7207 | likely_pathogenic | 0.7258 | pathogenic | 0.311 | Stabilizing | 0.992 | D | 0.824 | 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.