Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21302 | 64129;64130;64131 | chr2:178587307;178587306;178587305 | chr2:179452034;179452033;179452032 |
| N2AB | 19661 | 59206;59207;59208 | chr2:178587307;178587306;178587305 | chr2:179452034;179452033;179452032 |
| N2A | 18734 | 56425;56426;56427 | chr2:178587307;178587306;178587305 | chr2:179452034;179452033;179452032 |
| N2B | 12237 | 36934;36935;36936 | chr2:178587307;178587306;178587305 | chr2:179452034;179452033;179452032 |
| Novex-1 | 12362 | 37309;37310;37311 | chr2:178587307;178587306;178587305 | chr2:179452034;179452033;179452032 |
| Novex-2 | 12429 | 37510;37511;37512 | chr2:178587307;178587306;178587305 | chr2:179452034;179452033;179452032 |
| 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/N | rs1228375240  |
None | 0.999 | N | 0.759 | 0.412 | 0.788716532118 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs1228375240 |
None | 0.999 | N | 0.759 | 0.412 | 0.788716532118 | gnomAD-4.0.0 | 6.57912E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47145E-05 | 0 | 0 |
| I/V | None | None | 0.333 | N | 0.242 | 0.062 | 0.424670345773 | gnomAD-4.0.0 | 6.84514E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99698E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4024 | ambiguous | 0.4412 | ambiguous | -2.638 | Highly Destabilizing | 0.992 | D | 0.56 | neutral | None | None | None | None | N |
| I/C | 0.6455 | likely_pathogenic | 0.6934 | pathogenic | -1.998 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| I/D | 0.9042 | likely_pathogenic | 0.9134 | pathogenic | -3.362 | Highly Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| I/E | 0.7725 | likely_pathogenic | 0.7863 | pathogenic | -3.199 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/F | 0.2279 | likely_benign | 0.232 | benign | -1.503 | Destabilizing | 0.998 | D | 0.629 | neutral | N | 0.465506208 | None | None | N |
| I/G | 0.8238 | likely_pathogenic | 0.8431 | pathogenic | -3.078 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/H | 0.569 | likely_pathogenic | 0.5816 | pathogenic | -2.495 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/K | 0.588 | likely_pathogenic | 0.5827 | pathogenic | -2.106 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/L | 0.1255 | likely_benign | 0.1363 | benign | -1.372 | Destabilizing | 0.889 | D | 0.397 | neutral | N | 0.51622793 | None | None | N |
| I/M | 0.1145 | likely_benign | 0.1305 | benign | -1.389 | Destabilizing | 0.999 | D | 0.639 | neutral | N | 0.480585496 | None | None | N |
| I/N | 0.5168 | ambiguous | 0.5283 | ambiguous | -2.36 | Highly Destabilizing | 0.999 | D | 0.759 | deleterious | N | 0.469492226 | None | None | N |
| I/P | 0.9865 | likely_pathogenic | 0.9901 | pathogenic | -1.779 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/Q | 0.5882 | likely_pathogenic | 0.5885 | pathogenic | -2.307 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| I/R | 0.4575 | ambiguous | 0.4507 | ambiguous | -1.656 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| I/S | 0.4079 | ambiguous | 0.4239 | ambiguous | -2.892 | Highly Destabilizing | 0.998 | D | 0.68 | prob.neutral | N | 0.469706036 | None | None | N |
| I/T | 0.1835 | likely_benign | 0.2138 | benign | -2.622 | Highly Destabilizing | 0.989 | D | 0.599 | neutral | N | 0.495948659 | None | None | N |
| I/V | 0.0757 | likely_benign | 0.0809 | benign | -1.779 | Destabilizing | 0.333 | N | 0.242 | neutral | N | 0.468090054 | None | None | N |
| I/W | 0.7994 | likely_pathogenic | 0.8439 | pathogenic | -1.935 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/Y | 0.5791 | likely_pathogenic | 0.5786 | pathogenic | -1.747 | Destabilizing | 1.0 | D | 0.671 | 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.