Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27985 | 84178;84179;84180 | chr2:178562179;178562178;178562177 | chr2:179426906;179426905;179426904 |
| N2AB | 26344 | 79255;79256;79257 | chr2:178562179;178562178;178562177 | chr2:179426906;179426905;179426904 |
| N2A | 25417 | 76474;76475;76476 | chr2:178562179;178562178;178562177 | chr2:179426906;179426905;179426904 |
| N2B | 18920 | 56983;56984;56985 | chr2:178562179;178562178;178562177 | chr2:179426906;179426905;179426904 |
| Novex-1 | 19045 | 57358;57359;57360 | chr2:178562179;178562178;178562177 | chr2:179426906;179426905;179426904 |
| Novex-2 | 19112 | 57559;57560;57561 | chr2:178562179;178562178;178562177 | chr2:179426906;179426905;179426904 |
| 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/L | rs978568900  |
None | 0.988 | N | 0.781 | 0.5 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs978568900 |
None | 0.988 | N | 0.781 | 0.5 | None | gnomAD-4.0.0 | 3.1001E-06 | None | None | None | None | N | None | 2.67208E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54345E-06 | 0 | 0 |
| P/Q | None | None | 0.988 | N | 0.801 | 0.436 | 0.494769474416 | gnomAD-4.0.0 | 6.84578E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99685E-07 | 0 | 0 |
| P/S | rs1362226750 |
-1.615 | 0.988 | N | 0.734 | 0.44 | 0.472181857204 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1362226750 |
-1.615 | 0.988 | N | 0.734 | 0.44 | 0.472181857204 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1362226750 |
-1.615 | 0.988 | N | 0.734 | 0.44 | 0.472181857204 | gnomAD-4.0.0 | 1.86011E-06 | None | None | None | None | N | None | 4.00855E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1511 | likely_benign | 0.1736 | benign | -1.471 | Destabilizing | 0.958 | D | 0.606 | neutral | N | 0.506301799 | None | None | N |
| P/C | 0.6572 | likely_pathogenic | 0.6998 | pathogenic | -0.965 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| P/D | 0.7436 | likely_pathogenic | 0.7569 | pathogenic | -1.631 | Destabilizing | 0.995 | D | 0.804 | deleterious | None | None | None | None | N |
| P/E | 0.5589 | ambiguous | 0.5958 | pathogenic | -1.562 | Destabilizing | 0.991 | D | 0.743 | deleterious | None | None | None | None | N |
| P/F | 0.6364 | likely_pathogenic | 0.7062 | pathogenic | -0.94 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| P/G | 0.5414 | ambiguous | 0.5998 | pathogenic | -1.85 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/H | 0.3301 | likely_benign | 0.3667 | ambiguous | -1.505 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| P/I | 0.3724 | ambiguous | 0.4102 | ambiguous | -0.502 | Destabilizing | 0.995 | D | 0.806 | deleterious | None | None | None | None | N |
| P/K | 0.4828 | ambiguous | 0.5155 | ambiguous | -1.391 | Destabilizing | 0.938 | D | 0.71 | prob.delet. | None | None | None | None | N |
| P/L | 0.1789 | likely_benign | 0.213 | benign | -0.502 | Destabilizing | 0.988 | D | 0.781 | deleterious | N | 0.519179042 | None | None | N |
| P/M | 0.4913 | ambiguous | 0.5414 | ambiguous | -0.412 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| P/N | 0.5403 | ambiguous | 0.5645 | pathogenic | -1.341 | Destabilizing | 0.991 | D | 0.779 | deleterious | None | None | None | None | N |
| P/Q | 0.3078 | likely_benign | 0.3514 | ambiguous | -1.405 | Destabilizing | 0.988 | D | 0.801 | deleterious | N | 0.498704475 | None | None | N |
| P/R | 0.2938 | likely_benign | 0.3355 | benign | -0.961 | Destabilizing | 0.142 | N | 0.527 | neutral | N | 0.494692004 | None | None | N |
| P/S | 0.2518 | likely_benign | 0.2893 | benign | -1.845 | Destabilizing | 0.988 | D | 0.734 | prob.delet. | N | 0.508187903 | None | None | N |
| P/T | 0.1828 | likely_benign | 0.2033 | benign | -1.666 | Destabilizing | 0.988 | D | 0.767 | deleterious | N | 0.496930049 | None | None | N |
| P/V | 0.2795 | likely_benign | 0.3098 | benign | -0.792 | Destabilizing | 0.995 | D | 0.777 | deleterious | None | None | None | None | N |
| P/W | 0.8148 | likely_pathogenic | 0.8656 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/Y | 0.6092 | likely_pathogenic | 0.6586 | pathogenic | -0.939 | Destabilizing | 1.0 | D | 0.799 | 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.