Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16391 | 49396;49397;49398 | chr2:178614226;178614225;178614224 | chr2:179478953;179478952;179478951 |
| N2AB | 14750 | 44473;44474;44475 | chr2:178614226;178614225;178614224 | chr2:179478953;179478952;179478951 |
| N2A | 13823 | 41692;41693;41694 | chr2:178614226;178614225;178614224 | chr2:179478953;179478952;179478951 |
| N2B | 7326 | 22201;22202;22203 | chr2:178614226;178614225;178614224 | chr2:179478953;179478952;179478951 |
| Novex-1 | 7451 | 22576;22577;22578 | chr2:178614226;178614225;178614224 | chr2:179478953;179478952;179478951 |
| Novex-2 | 7518 | 22777;22778;22779 | chr2:178614226;178614225;178614224 | chr2:179478953;179478952;179478951 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs200944827  |
-1.214 | 0.271 | D | 0.478 | 0.191 | None | gnomAD-2.1.1 | 1.29208E-04 | None | None | None | None | N | None | 4.14E-05 | 2.55638E-04 | None | 0 | 4.17493E-04 | None | 0 | None | 0 | 1.2584E-04 | 2.82008E-04 |
| R/Q | rs200944827 |
-1.214 | 0.271 | D | 0.478 | 0.191 | None | gnomAD-3.1.2 | 1.31737E-04 | None | None | None | None | N | None | 9.67E-05 | 4.60163E-04 | 0 | 0 | 3.90625E-04 | None | 0 | 0 | 1.03093E-04 | 0 | 0 |
| R/Q | rs200944827 |
-1.214 | 0.271 | D | 0.478 | 0.191 | None | gnomAD-4.0.0 | 1.60631E-04 | None | None | None | None | N | None | 5.34845E-05 | 2.8411E-04 | None | 0 | 1.79582E-04 | None | 0 | 0 | 1.84861E-04 | 4.39338E-05 | 1.28254E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7881 | likely_pathogenic | 0.7869 | pathogenic | -2.089 | Highly Destabilizing | 0.035 | N | 0.483 | neutral | None | None | None | None | N |
| R/C | 0.2622 | likely_benign | 0.2067 | benign | -2.062 | Highly Destabilizing | 0.935 | D | 0.659 | neutral | None | None | None | None | N |
| R/D | 0.9851 | likely_pathogenic | 0.9848 | pathogenic | -0.896 | Destabilizing | 0.149 | N | 0.577 | neutral | None | None | None | None | N |
| R/E | 0.8092 | likely_pathogenic | 0.8169 | pathogenic | -0.701 | Destabilizing | 0.035 | N | 0.506 | neutral | None | None | None | None | N |
| R/F | 0.8671 | likely_pathogenic | 0.8605 | pathogenic | -1.549 | Destabilizing | 0.791 | D | 0.639 | neutral | None | None | None | None | N |
| R/G | 0.76 | likely_pathogenic | 0.7504 | pathogenic | -2.42 | Highly Destabilizing | 0.251 | N | 0.528 | neutral | D | 0.634451498 | None | None | N |
| R/H | 0.3288 | likely_benign | 0.3007 | benign | -2.272 | Highly Destabilizing | 0.555 | D | 0.429 | neutral | None | None | None | None | N |
| R/I | 0.71 | likely_pathogenic | 0.6956 | pathogenic | -1.136 | Destabilizing | 0.555 | D | 0.637 | neutral | None | None | None | None | N |
| R/K | 0.1052 | likely_benign | 0.1166 | benign | -1.514 | Destabilizing | None | N | 0.127 | neutral | None | None | None | None | N |
| R/L | 0.5817 | likely_pathogenic | 0.5816 | pathogenic | -1.136 | Destabilizing | 0.251 | N | 0.528 | neutral | D | 0.589763767 | None | None | N |
| R/M | 0.483 | ambiguous | 0.5099 | ambiguous | -1.526 | Destabilizing | 0.791 | D | 0.509 | neutral | None | None | None | None | N |
| R/N | 0.9316 | likely_pathogenic | 0.9297 | pathogenic | -1.315 | Destabilizing | 0.149 | N | 0.447 | neutral | None | None | None | None | N |
| R/P | 0.994 | likely_pathogenic | 0.9941 | pathogenic | -1.442 | Destabilizing | 0.705 | D | 0.579 | neutral | D | 0.746319342 | None | None | N |
| R/Q | 0.1768 | likely_benign | 0.1801 | benign | -1.323 | Destabilizing | 0.271 | N | 0.478 | neutral | D | 0.537512877 | None | None | N |
| R/S | 0.8948 | likely_pathogenic | 0.883 | pathogenic | -2.317 | Highly Destabilizing | 0.081 | N | 0.473 | neutral | None | None | None | None | N |
| R/T | 0.7812 | likely_pathogenic | 0.7805 | pathogenic | -1.912 | Destabilizing | 0.149 | N | 0.475 | neutral | None | None | None | None | N |
| R/V | 0.7455 | likely_pathogenic | 0.73 | pathogenic | -1.442 | Destabilizing | 0.38 | N | 0.6 | neutral | None | None | None | None | N |
| R/W | 0.6363 | likely_pathogenic | 0.6222 | pathogenic | -1.014 | Destabilizing | 0.935 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/Y | 0.7877 | likely_pathogenic | 0.7668 | pathogenic | -0.847 | Destabilizing | 0.791 | D | 0.603 | 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.