Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30237 | 90934;90935;90936 | chr2:178552191;178552190;178552189 | chr2:179416918;179416917;179416916 |
| N2AB | 28596 | 86011;86012;86013 | chr2:178552191;178552190;178552189 | chr2:179416918;179416917;179416916 |
| N2A | 27669 | 83230;83231;83232 | chr2:178552191;178552190;178552189 | chr2:179416918;179416917;179416916 |
| N2B | 21172 | 63739;63740;63741 | chr2:178552191;178552190;178552189 | chr2:179416918;179416917;179416916 |
| Novex-1 | 21297 | 64114;64115;64116 | chr2:178552191;178552190;178552189 | chr2:179416918;179416917;179416916 |
| Novex-2 | 21364 | 64315;64316;64317 | chr2:178552191;178552190;178552189 | chr2:179416918;179416917;179416916 |
| 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/V | rs370272916  |
-1.214 | 0.006 | N | 0.205 | 0.083 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| I/V | rs370272916 |
-1.214 | 0.006 | N | 0.205 | 0.083 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| I/V | rs370272916 |
-1.214 | 0.006 | N | 0.205 | 0.083 | None | gnomAD-4.0.0 | 1.67325E-05 | None | None | None | None | N | None | 0 | 1.66789E-05 | None | 0 | 0 | None | 0 | 0 | 2.11904E-05 | 0 | 1.60108E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7662 | likely_pathogenic | 0.669 | pathogenic | -1.712 | Destabilizing | 0.754 | D | 0.48 | neutral | None | None | None | None | N |
| I/C | 0.788 | likely_pathogenic | 0.7512 | pathogenic | -1.218 | Destabilizing | 0.998 | D | 0.607 | neutral | None | None | None | None | N |
| I/D | 0.9528 | likely_pathogenic | 0.916 | pathogenic | -1.127 | Destabilizing | 0.993 | D | 0.748 | deleterious | None | None | None | None | N |
| I/E | 0.8226 | likely_pathogenic | 0.7617 | pathogenic | -1.109 | Destabilizing | 0.978 | D | 0.747 | deleterious | None | None | None | None | N |
| I/F | 0.4343 | ambiguous | 0.3741 | ambiguous | -1.187 | Destabilizing | 0.942 | D | 0.566 | neutral | N | 0.499725257 | None | None | N |
| I/G | 0.9221 | likely_pathogenic | 0.8678 | pathogenic | -2.054 | Highly Destabilizing | 0.978 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/H | 0.8727 | likely_pathogenic | 0.8232 | pathogenic | -1.332 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/K | 0.6707 | likely_pathogenic | 0.5827 | pathogenic | -1.178 | Destabilizing | 0.978 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/L | 0.2132 | likely_benign | 0.1901 | benign | -0.838 | Destabilizing | 0.294 | N | 0.329 | neutral | N | 0.499703827 | None | None | N |
| I/M | 0.1541 | likely_benign | 0.144 | benign | -0.745 | Destabilizing | 0.942 | D | 0.55 | neutral | N | 0.477475305 | None | None | N |
| I/N | 0.6678 | likely_pathogenic | 0.5422 | ambiguous | -1.012 | Destabilizing | 0.99 | D | 0.739 | prob.delet. | N | 0.479183599 | None | None | N |
| I/P | 0.9631 | likely_pathogenic | 0.9019 | pathogenic | -1.098 | Destabilizing | 0.993 | D | 0.753 | deleterious | None | None | None | None | N |
| I/Q | 0.7252 | likely_pathogenic | 0.6543 | pathogenic | -1.171 | Destabilizing | 0.993 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/R | 0.6538 | likely_pathogenic | 0.5533 | ambiguous | -0.653 | Destabilizing | 0.978 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/S | 0.7568 | likely_pathogenic | 0.6511 | pathogenic | -1.663 | Destabilizing | 0.942 | D | 0.658 | neutral | N | 0.513134484 | None | None | N |
| I/T | 0.5841 | likely_pathogenic | 0.4847 | ambiguous | -1.523 | Destabilizing | 0.822 | D | 0.548 | neutral | N | 0.50085862 | None | None | N |
| I/V | 0.0885 | likely_benign | 0.0772 | benign | -1.098 | Destabilizing | 0.006 | N | 0.205 | neutral | N | 0.367272486 | None | None | N |
| I/W | 0.9163 | likely_pathogenic | 0.9043 | pathogenic | -1.254 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7799 | likely_pathogenic | 0.7296 | pathogenic | -1.026 | Destabilizing | 0.978 | D | 0.644 | 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.