Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33422 | 100489;100490;100491 | chr2:178536483;178536482;178536481 | chr2:179401210;179401209;179401208 |
| N2AB | 31781 | 95566;95567;95568 | chr2:178536483;178536482;178536481 | chr2:179401210;179401209;179401208 |
| N2A | 30854 | 92785;92786;92787 | chr2:178536483;178536482;178536481 | chr2:179401210;179401209;179401208 |
| N2B | 24357 | 73294;73295;73296 | chr2:178536483;178536482;178536481 | chr2:179401210;179401209;179401208 |
| Novex-1 | 24482 | 73669;73670;73671 | chr2:178536483;178536482;178536481 | chr2:179401210;179401209;179401208 |
| Novex-2 | 24549 | 73870;73871;73872 | chr2:178536483;178536482;178536481 | chr2:179401210;179401209;179401208 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs1191954484  |
-0.784 | 0.993 | N | 0.767 | 0.424 | 0.496560916508 | gnomAD-2.1.1 | 4.46E-06 | None | None | None | None | I | None | 0 | 3.14E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/E | rs1191954484 |
-0.784 | 0.993 | N | 0.767 | 0.424 | 0.496560916508 | gnomAD-4.0.0 | 1.6743E-06 | None | None | None | None | I | None | 0 | 2.44654E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs1419201312 |
-0.779 | 0.955 | N | 0.651 | 0.163 | 0.359763055319 | gnomAD-2.1.1 | 4.56E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.87E-06 | 0 |
| A/T | rs1419201312 |
-0.779 | 0.955 | N | 0.651 | 0.163 | 0.359763055319 | gnomAD-4.0.0 | 7.01749E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.14461E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6279 | likely_pathogenic | 0.6839 | pathogenic | -0.823 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| A/D | 0.819 | likely_pathogenic | 0.849 | pathogenic | -0.511 | Destabilizing | 0.995 | D | 0.833 | deleterious | None | None | None | None | I |
| A/E | 0.7555 | likely_pathogenic | 0.7788 | pathogenic | -0.646 | Destabilizing | 0.993 | D | 0.767 | deleterious | N | 0.517806798 | None | None | I |
| A/F | 0.7488 | likely_pathogenic | 0.7632 | pathogenic | -1.082 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | I |
| A/G | 0.3062 | likely_benign | 0.3221 | benign | -0.655 | Destabilizing | 0.955 | D | 0.571 | neutral | N | 0.497407309 | None | None | I |
| A/H | 0.8563 | likely_pathogenic | 0.8738 | pathogenic | -0.695 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| A/I | 0.8139 | likely_pathogenic | 0.7927 | pathogenic | -0.469 | Destabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | I |
| A/K | 0.9253 | likely_pathogenic | 0.9277 | pathogenic | -0.735 | Destabilizing | 0.995 | D | 0.767 | deleterious | None | None | None | None | I |
| A/L | 0.5951 | likely_pathogenic | 0.5738 | pathogenic | -0.469 | Destabilizing | 0.983 | D | 0.732 | prob.delet. | None | None | None | None | I |
| A/M | 0.6382 | likely_pathogenic | 0.6189 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| A/N | 0.6064 | likely_pathogenic | 0.6474 | pathogenic | -0.385 | Destabilizing | 0.995 | D | 0.835 | deleterious | None | None | None | None | I |
| A/P | 0.9778 | likely_pathogenic | 0.971 | pathogenic | -0.461 | Destabilizing | 0.997 | D | 0.791 | deleterious | N | 0.489930793 | None | None | I |
| A/Q | 0.7212 | likely_pathogenic | 0.7324 | pathogenic | -0.678 | Destabilizing | 0.998 | D | 0.793 | deleterious | None | None | None | None | I |
| A/R | 0.8589 | likely_pathogenic | 0.8593 | pathogenic | -0.289 | Destabilizing | 0.995 | D | 0.789 | deleterious | None | None | None | None | I |
| A/S | 0.1158 | likely_benign | 0.1269 | benign | -0.674 | Destabilizing | 0.362 | N | 0.471 | neutral | N | 0.378873559 | None | None | I |
| A/T | 0.2505 | likely_benign | 0.2331 | benign | -0.726 | Destabilizing | 0.955 | D | 0.651 | neutral | N | 0.486619886 | None | None | I |
| A/V | 0.5104 | ambiguous | 0.4819 | ambiguous | -0.461 | Destabilizing | 0.977 | D | 0.757 | deleterious | N | 0.518326873 | None | None | I |
| A/W | 0.9612 | likely_pathogenic | 0.9644 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| A/Y | 0.8566 | likely_pathogenic | 0.873 | pathogenic | -0.86 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | I |
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.