Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23362 | 70309;70310;70311 | chr2:178576048;178576047;178576046 | chr2:179440775;179440774;179440773 |
| N2AB | 21721 | 65386;65387;65388 | chr2:178576048;178576047;178576046 | chr2:179440775;179440774;179440773 |
| N2A | 20794 | 62605;62606;62607 | chr2:178576048;178576047;178576046 | chr2:179440775;179440774;179440773 |
| N2B | 14297 | 43114;43115;43116 | chr2:178576048;178576047;178576046 | chr2:179440775;179440774;179440773 |
| Novex-1 | 14422 | 43489;43490;43491 | chr2:178576048;178576047;178576046 | chr2:179440775;179440774;179440773 |
| Novex-2 | 14489 | 43690;43691;43692 | chr2:178576048;178576047;178576046 | chr2:179440775;179440774;179440773 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs372048460  |
-0.787 | 0.002 | N | 0.259 | 0.163 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/L | rs372048460 |
-0.787 | 0.002 | N | 0.259 | 0.163 | None | gnomAD-4.0.0 | 5.47447E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19665E-06 | 0 | 0 |
| I/T | rs750943570 |
-2.109 | 0.643 | N | 0.695 | 0.386 | 0.53837629882 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs750943570 |
-2.109 | 0.643 | N | 0.695 | 0.386 | 0.53837629882 | gnomAD-4.0.0 | 2.05292E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99582E-07 | 2.31906E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9134 | likely_pathogenic | 0.9316 | pathogenic | -2.865 | Highly Destabilizing | 0.496 | N | 0.617 | neutral | None | None | None | None | N |
| I/C | 0.944 | likely_pathogenic | 0.9533 | pathogenic | -2.208 | Highly Destabilizing | 0.995 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/D | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -3.046 | Highly Destabilizing | 0.981 | D | 0.791 | deleterious | None | None | None | None | N |
| I/E | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -2.802 | Highly Destabilizing | 0.944 | D | 0.791 | deleterious | None | None | None | None | N |
| I/F | 0.73 | likely_pathogenic | 0.7326 | pathogenic | -1.745 | Destabilizing | 0.863 | D | 0.675 | neutral | N | 0.469369772 | None | None | N |
| I/G | 0.9934 | likely_pathogenic | 0.9953 | pathogenic | -3.44 | Highly Destabilizing | 0.944 | D | 0.782 | deleterious | None | None | None | None | N |
| I/H | 0.9972 | likely_pathogenic | 0.9975 | pathogenic | -2.705 | Highly Destabilizing | 0.995 | D | 0.775 | deleterious | None | None | None | None | N |
| I/K | 0.9961 | likely_pathogenic | 0.9965 | pathogenic | -2.42 | Highly Destabilizing | 0.944 | D | 0.781 | deleterious | None | None | None | None | N |
| I/L | 0.2212 | likely_benign | 0.225 | benign | -1.192 | Destabilizing | 0.002 | N | 0.259 | neutral | N | 0.448740997 | None | None | N |
| I/M | 0.303 | likely_benign | 0.3239 | benign | -1.093 | Destabilizing | 0.863 | D | 0.669 | neutral | N | 0.488744967 | None | None | N |
| I/N | 0.9913 | likely_pathogenic | 0.9931 | pathogenic | -2.795 | Highly Destabilizing | 0.975 | D | 0.784 | deleterious | N | 0.48438266 | None | None | N |
| I/P | 0.9949 | likely_pathogenic | 0.9957 | pathogenic | -1.732 | Destabilizing | 0.981 | D | 0.784 | deleterious | None | None | None | None | N |
| I/Q | 0.995 | likely_pathogenic | 0.9955 | pathogenic | -2.641 | Highly Destabilizing | 0.981 | D | 0.792 | deleterious | None | None | None | None | N |
| I/R | 0.9935 | likely_pathogenic | 0.9944 | pathogenic | -2.065 | Highly Destabilizing | 0.944 | D | 0.787 | deleterious | None | None | None | None | N |
| I/S | 0.9756 | likely_pathogenic | 0.9822 | pathogenic | -3.545 | Highly Destabilizing | 0.928 | D | 0.745 | deleterious | N | 0.472772865 | None | None | N |
| I/T | 0.9637 | likely_pathogenic | 0.9731 | pathogenic | -3.139 | Highly Destabilizing | 0.643 | D | 0.695 | prob.neutral | N | 0.465682521 | None | None | N |
| I/V | 0.1524 | likely_benign | 0.1577 | benign | -1.732 | Destabilizing | 0.14 | N | 0.389 | neutral | N | 0.449719645 | None | None | N |
| I/W | 0.9955 | likely_pathogenic | 0.9957 | pathogenic | -2.059 | Highly Destabilizing | 0.995 | D | 0.776 | deleterious | None | None | None | None | N |
| I/Y | 0.9812 | likely_pathogenic | 0.9828 | pathogenic | -1.82 | Destabilizing | 0.944 | D | 0.769 | 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.