Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31235 | 93928;93929;93930 | chr2:178547923;178547922;178547921 | chr2:179412650;179412649;179412648 |
| N2AB | 29594 | 89005;89006;89007 | chr2:178547923;178547922;178547921 | chr2:179412650;179412649;179412648 |
| N2A | 28667 | 86224;86225;86226 | chr2:178547923;178547922;178547921 | chr2:179412650;179412649;179412648 |
| N2B | 22170 | 66733;66734;66735 | chr2:178547923;178547922;178547921 | chr2:179412650;179412649;179412648 |
| Novex-1 | 22295 | 67108;67109;67110 | chr2:178547923;178547922;178547921 | chr2:179412650;179412649;179412648 |
| Novex-2 | 22362 | 67309;67310;67311 | chr2:178547923;178547922;178547921 | chr2:179412650;179412649;179412648 |
| 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/F | rs373782488  |
-1.51 | 0.89 | N | 0.697 | 0.225 | None | 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 |
| I/M | rs1697879569 |
None | 0.942 | N | 0.674 | 0.326 | 0.335661160332 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs1697879569 |
None | 0.942 | N | 0.674 | 0.326 | 0.335661160332 | gnomAD-4.0.0 | 3.09843E-06 | None | None | None | None | N | None | 6.67503E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | None | None | 0.99 | N | 0.845 | 0.555 | 0.895285619443 | gnomAD-4.0.0 | 6.84191E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99429E-07 | 0 | 0 |
| I/T | rs1246425366 |
-2.482 | 0.942 | N | 0.754 | 0.537 | 0.760694194147 | 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 |
| I/T | rs1246425366 |
-2.482 | 0.942 | N | 0.754 | 0.537 | 0.760694194147 | gnomAD-4.0.0 | 7.5261E-06 | None | None | None | None | N | None | 0 | 2.23654E-05 | None | 0 | 0 | None | 0 | 0 | 8.99429E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.751 | likely_pathogenic | 0.7898 | pathogenic | -1.858 | Destabilizing | 0.86 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/C | 0.9555 | likely_pathogenic | 0.9551 | pathogenic | -1.505 | Destabilizing | 0.998 | D | 0.72 | prob.delet. | None | None | None | None | N |
| I/D | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -2.53 | Highly Destabilizing | 0.993 | D | 0.842 | deleterious | None | None | None | None | N |
| I/E | 0.9953 | likely_pathogenic | 0.9953 | pathogenic | -2.24 | Highly Destabilizing | 0.978 | D | 0.844 | deleterious | None | None | None | None | N |
| I/F | 0.5921 | likely_pathogenic | 0.5625 | ambiguous | -1.226 | Destabilizing | 0.89 | D | 0.697 | prob.neutral | N | 0.488929473 | None | None | N |
| I/G | 0.9884 | likely_pathogenic | 0.9899 | pathogenic | -2.385 | Highly Destabilizing | 0.978 | D | 0.848 | deleterious | None | None | None | None | N |
| I/H | 0.9959 | likely_pathogenic | 0.9953 | pathogenic | -2.388 | Highly Destabilizing | 0.998 | D | 0.819 | deleterious | None | None | None | None | N |
| I/K | 0.9927 | likely_pathogenic | 0.9919 | pathogenic | -1.532 | Destabilizing | 0.978 | D | 0.844 | deleterious | None | None | None | None | N |
| I/L | 0.2067 | likely_benign | 0.2017 | benign | -0.286 | Destabilizing | 0.006 | N | 0.273 | neutral | N | 0.402867926 | None | None | N |
| I/M | 0.2259 | likely_benign | 0.2105 | benign | -0.587 | Destabilizing | 0.942 | D | 0.674 | neutral | N | 0.52124504 | None | None | N |
| I/N | 0.9897 | likely_pathogenic | 0.989 | pathogenic | -2.177 | Highly Destabilizing | 0.99 | D | 0.845 | deleterious | N | 0.514307651 | None | None | N |
| I/P | 0.9922 | likely_pathogenic | 0.9928 | pathogenic | -0.799 | Destabilizing | 0.993 | D | 0.839 | deleterious | None | None | None | None | N |
| I/Q | 0.9926 | likely_pathogenic | 0.9923 | pathogenic | -1.763 | Destabilizing | 0.993 | D | 0.847 | deleterious | None | None | None | None | N |
| I/R | 0.9875 | likely_pathogenic | 0.9861 | pathogenic | -1.902 | Destabilizing | 0.978 | D | 0.833 | deleterious | None | None | None | None | N |
| I/S | 0.959 | likely_pathogenic | 0.9622 | pathogenic | -2.66 | Highly Destabilizing | 0.971 | D | 0.809 | deleterious | N | 0.514307651 | None | None | N |
| I/T | 0.8346 | likely_pathogenic | 0.8564 | pathogenic | -2.201 | Highly Destabilizing | 0.942 | D | 0.754 | deleterious | N | 0.514054161 | None | None | N |
| I/V | 0.0899 | likely_benign | 0.0906 | benign | -0.799 | Destabilizing | 0.294 | N | 0.416 | neutral | N | 0.490538131 | None | None | N |
| I/W | 0.9867 | likely_pathogenic | 0.9857 | pathogenic | -1.556 | Destabilizing | 0.998 | D | 0.811 | deleterious | None | None | None | None | N |
| I/Y | 0.9724 | likely_pathogenic | 0.9686 | pathogenic | -1.291 | Destabilizing | 0.978 | D | 0.734 | prob.delet. | 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.