Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21133 | 63622;63623;63624 | chr2:178588010;178588009;178588008 | chr2:179452737;179452736;179452735 |
| N2AB | 19492 | 58699;58700;58701 | chr2:178588010;178588009;178588008 | chr2:179452737;179452736;179452735 |
| N2A | 18565 | 55918;55919;55920 | chr2:178588010;178588009;178588008 | chr2:179452737;179452736;179452735 |
| N2B | 12068 | 36427;36428;36429 | chr2:178588010;178588009;178588008 | chr2:179452737;179452736;179452735 |
| Novex-1 | 12193 | 36802;36803;36804 | chr2:178588010;178588009;178588008 | chr2:179452737;179452736;179452735 |
| Novex-2 | 12260 | 37003;37004;37005 | chr2:178588010;178588009;178588008 | chr2:179452737;179452736;179452735 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs766276741  |
-0.503 | 0.704 | N | 0.352 | 0.174 | 0.227934060464 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| T/A | rs766276741 |
-0.503 | 0.704 | N | 0.352 | 0.174 | 0.227934060464 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs766276741 |
-0.503 | 0.704 | N | 0.352 | 0.174 | 0.227934060464 | gnomAD-4.0.0 | 3.10019E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23953E-06 | 0 | 0 |
| T/I | rs1576043145 |
None | 0.988 | N | 0.547 | 0.281 | None | gnomAD-4.0.0 | 1.36918E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99766E-07 | 0 | 1.65761E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0893 | likely_benign | 0.0936 | benign | -0.464 | Destabilizing | 0.704 | D | 0.352 | neutral | N | 0.472853723 | None | None | N |
| T/C | 0.3986 | ambiguous | 0.3907 | ambiguous | -0.282 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| T/D | 0.3792 | ambiguous | 0.3783 | ambiguous | 0.437 | Stabilizing | 0.884 | D | 0.446 | neutral | None | None | None | None | N |
| T/E | 0.3234 | likely_benign | 0.3141 | benign | 0.369 | Stabilizing | 0.939 | D | 0.445 | neutral | None | None | None | None | N |
| T/F | 0.2888 | likely_benign | 0.2887 | benign | -0.952 | Destabilizing | 0.997 | D | 0.587 | neutral | None | None | None | None | N |
| T/G | 0.1897 | likely_benign | 0.1926 | benign | -0.598 | Destabilizing | 0.02 | N | 0.296 | neutral | None | None | None | None | N |
| T/H | 0.2725 | likely_benign | 0.258 | benign | -0.885 | Destabilizing | 0.991 | D | 0.571 | neutral | None | None | None | None | N |
| T/I | 0.2 | likely_benign | 0.1976 | benign | -0.23 | Destabilizing | 0.988 | D | 0.547 | neutral | N | 0.475767012 | None | None | N |
| T/K | 0.2109 | likely_benign | 0.2031 | benign | -0.274 | Destabilizing | 0.939 | D | 0.447 | neutral | None | None | None | None | N |
| T/L | 0.0971 | likely_benign | 0.0955 | benign | -0.23 | Destabilizing | 0.969 | D | 0.444 | neutral | None | None | None | None | N |
| T/M | 0.0973 | likely_benign | 0.0975 | benign | -0.041 | Destabilizing | 0.999 | D | 0.511 | neutral | None | None | None | None | N |
| T/N | 0.1211 | likely_benign | 0.1224 | benign | -0.086 | Destabilizing | 0.134 | N | 0.195 | neutral | N | 0.508939386 | None | None | N |
| T/P | 0.0861 | likely_benign | 0.0819 | benign | -0.28 | Destabilizing | 0.988 | D | 0.545 | neutral | N | 0.521945968 | None | None | N |
| T/Q | 0.2188 | likely_benign | 0.2064 | benign | -0.292 | Destabilizing | 0.991 | D | 0.542 | neutral | None | None | None | None | N |
| T/R | 0.2062 | likely_benign | 0.1987 | benign | -0.051 | Destabilizing | 0.991 | D | 0.539 | neutral | None | None | None | None | N |
| T/S | 0.1096 | likely_benign | 0.1093 | benign | -0.358 | Destabilizing | 0.31 | N | 0.174 | neutral | N | 0.46732205 | None | None | N |
| T/V | 0.1542 | likely_benign | 0.1472 | benign | -0.28 | Destabilizing | 0.969 | D | 0.347 | neutral | None | None | None | None | N |
| T/W | 0.648 | likely_pathogenic | 0.6434 | pathogenic | -0.929 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| T/Y | 0.3115 | likely_benign | 0.3117 | benign | -0.645 | Destabilizing | 0.997 | D | 0.575 | 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.