Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23897 | 71914;71915;71916 | chr2:178574443;178574442;178574441 | chr2:179439170;179439169;179439168 |
| N2AB | 22256 | 66991;66992;66993 | chr2:178574443;178574442;178574441 | chr2:179439170;179439169;179439168 |
| N2A | 21329 | 64210;64211;64212 | chr2:178574443;178574442;178574441 | chr2:179439170;179439169;179439168 |
| N2B | 14832 | 44719;44720;44721 | chr2:178574443;178574442;178574441 | chr2:179439170;179439169;179439168 |
| Novex-1 | 14957 | 45094;45095;45096 | chr2:178574443;178574442;178574441 | chr2:179439170;179439169;179439168 |
| Novex-2 | 15024 | 45295;45296;45297 | chr2:178574443;178574442;178574441 | chr2:179439170;179439169;179439168 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 1.0 | D | 0.873 | 0.923 | 0.871944566495 | gnomAD-4.0.0 | 3.18341E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 6.04997E-05 |
| Y/F | rs1457146309  |
-0.694 | 0.999 | D | 0.741 | 0.902 | 0.849883860545 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| Y/F | rs1457146309 |
-0.694 | 0.999 | D | 0.741 | 0.902 | 0.849883860545 | gnomAD-4.0.0 | 1.5917E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77285E-05 | None | 0 | 0 | 0 | 0 | 0 |
| Y/N | rs1338027065 |
-3.256 | 1.0 | D | 0.87 | 0.909 | 0.899771691189 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| Y/S | rs1457146309 |
-3.604 | 1.0 | D | 0.879 | 0.913 | 0.885317860142 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/S | rs1457146309 |
-3.604 | 1.0 | D | 0.879 | 0.913 | 0.885317860142 | gnomAD-4.0.0 | 3.18341E-06 | None | None | None | None | N | None | 0 | 4.57289E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9827 | likely_pathogenic | 0.9799 | pathogenic | -3.109 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| Y/C | 0.6852 | likely_pathogenic | 0.6355 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.662024156 | None | None | N |
| Y/D | 0.9905 | likely_pathogenic | 0.9887 | pathogenic | -3.404 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.694295043 | None | None | N |
| Y/E | 0.9956 | likely_pathogenic | 0.9949 | pathogenic | -3.215 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| Y/F | 0.2168 | likely_benign | 0.2494 | benign | -1.097 | Destabilizing | 0.999 | D | 0.741 | deleterious | D | 0.636759288 | None | None | N |
| Y/G | 0.9734 | likely_pathogenic | 0.969 | pathogenic | -3.491 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| Y/H | 0.9252 | likely_pathogenic | 0.917 | pathogenic | -2.001 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | D | 0.668756931 | None | None | N |
| Y/I | 0.9435 | likely_pathogenic | 0.9443 | pathogenic | -1.832 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/K | 0.9967 | likely_pathogenic | 0.9961 | pathogenic | -2.038 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| Y/L | 0.8964 | likely_pathogenic | 0.8985 | pathogenic | -1.832 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| Y/M | 0.957 | likely_pathogenic | 0.9582 | pathogenic | -1.473 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| Y/N | 0.9356 | likely_pathogenic | 0.9295 | pathogenic | -2.745 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | D | 0.677841713 | None | None | N |
| Y/P | 0.9971 | likely_pathogenic | 0.9963 | pathogenic | -2.272 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| Y/Q | 0.9928 | likely_pathogenic | 0.9915 | pathogenic | -2.565 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/R | 0.9857 | likely_pathogenic | 0.9826 | pathogenic | -1.705 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| Y/S | 0.9336 | likely_pathogenic | 0.9245 | pathogenic | -3.073 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.694295043 | None | None | N |
| Y/T | 0.9757 | likely_pathogenic | 0.9735 | pathogenic | -2.779 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| Y/V | 0.8443 | likely_pathogenic | 0.8419 | pathogenic | -2.272 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| Y/W | 0.665 | likely_pathogenic | 0.6458 | pathogenic | -0.409 | Destabilizing | 1.0 | D | 0.819 | 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.