Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28885 | 86878;86879;86880 | chr2:178559479;178559478;178559477 | chr2:179424206;179424205;179424204 |
| N2AB | 27244 | 81955;81956;81957 | chr2:178559479;178559478;178559477 | chr2:179424206;179424205;179424204 |
| N2A | 26317 | 79174;79175;79176 | chr2:178559479;178559478;178559477 | chr2:179424206;179424205;179424204 |
| N2B | 19820 | 59683;59684;59685 | chr2:178559479;178559478;178559477 | chr2:179424206;179424205;179424204 |
| Novex-1 | 19945 | 60058;60059;60060 | chr2:178559479;178559478;178559477 | chr2:179424206;179424205;179424204 |
| Novex-2 | 20012 | 60259;60260;60261 | chr2:178559479;178559478;178559477 | chr2:179424206;179424205;179424204 |
| 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/C | rs1702802682  |
None | 1.0 | D | 0.901 | 0.43 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| R/C | rs1702802682 |
None | 1.0 | D | 0.901 | 0.43 | None | gnomAD-4.0.0 | 3.09877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.68765E-05 | 0 | 1.6953E-06 | 0 | 0 |
| R/H | rs371539720 |
-2.547 | 1.0 | N | 0.766 | 0.492 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 2.89911E-04 | 0 | None | 0 | None | 0 | 3.9E-05 | 0 |
| R/H | rs371539720 |
-2.547 | 1.0 | N | 0.766 | 0.492 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 6.55E-05 | 0 | 2.88018E-04 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs371539720 |
-2.547 | 1.0 | N | 0.766 | 0.492 | None | gnomAD-4.0.0 | 3.40854E-05 | None | None | None | None | N | None | 2.6703E-05 | 3.334E-05 | None | 2.0273E-04 | 0 | None | 0 | 0 | 3.47537E-05 | 1.09803E-05 | 4.80338E-05 |
| R/L | rs371539720 |
-1.137 | 1.0 | N | 0.784 | 0.465 | 0.620522651735 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/L | rs371539720 |
-1.137 | 1.0 | N | 0.784 | 0.465 | 0.620522651735 | gnomAD-4.0.0 | 6.84255E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99518E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9909 | likely_pathogenic | 0.9882 | pathogenic | -2.189 | Highly Destabilizing | 1.0 | D | 0.548 | neutral | None | None | None | None | N |
| R/C | 0.7668 | likely_pathogenic | 0.7268 | pathogenic | -1.903 | Destabilizing | 1.0 | D | 0.901 | deleterious | D | 0.526333068 | None | None | N |
| R/D | 0.9992 | likely_pathogenic | 0.9989 | pathogenic | -0.916 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| R/E | 0.9838 | likely_pathogenic | 0.9786 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.531 | neutral | None | None | None | None | N |
| R/F | 0.9913 | likely_pathogenic | 0.9892 | pathogenic | -1.311 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/G | 0.9847 | likely_pathogenic | 0.9788 | pathogenic | -2.541 | Highly Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.500414952 | None | None | N |
| R/H | 0.7392 | likely_pathogenic | 0.7039 | pathogenic | -2.103 | Highly Destabilizing | 1.0 | D | 0.766 | deleterious | N | 0.485944775 | None | None | N |
| R/I | 0.9826 | likely_pathogenic | 0.9778 | pathogenic | -1.154 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| R/K | 0.3738 | ambiguous | 0.3448 | ambiguous | -1.197 | Destabilizing | 0.998 | D | 0.46 | neutral | None | None | None | None | N |
| R/L | 0.947 | likely_pathogenic | 0.9357 | pathogenic | -1.154 | Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.484512743 | None | None | N |
| R/M | 0.9561 | likely_pathogenic | 0.9425 | pathogenic | -1.61 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| R/N | 0.9965 | likely_pathogenic | 0.9959 | pathogenic | -1.289 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -1.49 | Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.523381053 | None | None | N |
| R/Q | 0.5888 | likely_pathogenic | 0.5328 | ambiguous | -1.189 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/S | 0.9971 | likely_pathogenic | 0.9959 | pathogenic | -2.28 | Highly Destabilizing | 1.0 | D | 0.782 | deleterious | N | 0.469229191 | None | None | N |
| R/T | 0.9932 | likely_pathogenic | 0.991 | pathogenic | -1.83 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/V | 0.9832 | likely_pathogenic | 0.9793 | pathogenic | -1.49 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| R/W | 0.8884 | likely_pathogenic | 0.859 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| R/Y | 0.963 | likely_pathogenic | 0.9542 | pathogenic | -0.653 | Destabilizing | 1.0 | D | 0.916 | 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.