Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29329 | 88210;88211;88212 | chr2:178557277;178557276;178557275 | chr2:179422004;179422003;179422002 |
| N2AB | 27688 | 83287;83288;83289 | chr2:178557277;178557276;178557275 | chr2:179422004;179422003;179422002 |
| N2A | 26761 | 80506;80507;80508 | chr2:178557277;178557276;178557275 | chr2:179422004;179422003;179422002 |
| N2B | 20264 | 61015;61016;61017 | chr2:178557277;178557276;178557275 | chr2:179422004;179422003;179422002 |
| Novex-1 | 20389 | 61390;61391;61392 | chr2:178557277;178557276;178557275 | chr2:179422004;179422003;179422002 |
| Novex-2 | 20456 | 61591;61592;61593 | chr2:178557277;178557276;178557275 | chr2:179422004;179422003;179422002 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.005 | N | 0.276 | 0.173 | 0.18274738541 | gnomAD-4.0.0 | 6.84196E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99421E-07 | 0 | 0 |
| P/L | rs777177198  |
-0.45 | 0.799 | N | 0.671 | 0.243 | 0.447410926215 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs777177198 |
-0.45 | 0.799 | N | 0.671 | 0.243 | 0.447410926215 | gnomAD-4.0.0 | 2.73678E-06 | None | None | None | None | I | None | 0 | 0 | None | 7.65345E-05 | 0 | None | 0 | 0 | 1.79884E-06 | 0 | 0 |
| P/S | rs376054748 |
None | 0.666 | N | 0.581 | 0.218 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs376054748 |
None | 0.666 | N | 0.581 | 0.218 | None | gnomAD-4.0.0 | 6.57134E-06 | None | None | None | None | I | None | 2.4122E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | None | None | 0.799 | N | 0.547 | 0.253 | 0.288352970974 | gnomAD-4.0.0 | 6.84196E-07 | None | None | None | None | I | None | 2.98704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0785 | likely_benign | 0.0803 | benign | -0.949 | Destabilizing | 0.005 | N | 0.276 | neutral | N | 0.470028707 | None | None | I |
| P/C | 0.5914 | likely_pathogenic | 0.6026 | pathogenic | -0.716 | Destabilizing | 0.993 | D | 0.741 | deleterious | None | None | None | None | I |
| P/D | 0.7334 | likely_pathogenic | 0.7327 | pathogenic | -0.707 | Destabilizing | 0.725 | D | 0.531 | neutral | None | None | None | None | I |
| P/E | 0.5242 | ambiguous | 0.5172 | ambiguous | -0.776 | Destabilizing | 0.066 | N | 0.261 | neutral | None | None | None | None | I |
| P/F | 0.6864 | likely_pathogenic | 0.6793 | pathogenic | -0.879 | Destabilizing | 0.974 | D | 0.755 | deleterious | None | None | None | None | I |
| P/G | 0.3425 | ambiguous | 0.3659 | ambiguous | -1.17 | Destabilizing | 0.725 | D | 0.598 | neutral | None | None | None | None | I |
| P/H | 0.4211 | ambiguous | 0.4292 | ambiguous | -0.669 | Destabilizing | 0.998 | D | 0.689 | prob.delet. | None | None | None | None | I |
| P/I | 0.5557 | ambiguous | 0.5522 | ambiguous | -0.482 | Destabilizing | 0.949 | D | 0.719 | prob.delet. | None | None | None | None | I |
| P/K | 0.642 | likely_pathogenic | 0.6428 | pathogenic | -0.872 | Destabilizing | 0.841 | D | 0.544 | neutral | None | None | None | None | I |
| P/L | 0.2586 | likely_benign | 0.2517 | benign | -0.482 | Destabilizing | 0.799 | D | 0.671 | prob.neutral | N | 0.515107636 | None | None | I |
| P/M | 0.4253 | ambiguous | 0.4299 | ambiguous | -0.44 | Destabilizing | 0.998 | D | 0.689 | prob.delet. | None | None | None | None | I |
| P/N | 0.5124 | ambiguous | 0.5224 | ambiguous | -0.567 | Destabilizing | 0.974 | D | 0.686 | prob.delet. | None | None | None | None | I |
| P/Q | 0.3208 | likely_benign | 0.3218 | benign | -0.793 | Destabilizing | 0.933 | D | 0.616 | neutral | N | 0.490910936 | None | None | I |
| P/R | 0.5055 | ambiguous | 0.4976 | ambiguous | -0.304 | Destabilizing | 0.933 | D | 0.649 | prob.neutral | N | 0.482517145 | None | None | I |
| P/S | 0.1823 | likely_benign | 0.1886 | benign | -0.989 | Destabilizing | 0.666 | D | 0.581 | neutral | N | 0.49117477 | None | None | I |
| P/T | 0.1847 | likely_benign | 0.1858 | benign | -0.954 | Destabilizing | 0.799 | D | 0.547 | neutral | N | 0.472046212 | None | None | I |
| P/V | 0.355 | ambiguous | 0.3537 | ambiguous | -0.602 | Destabilizing | 0.725 | D | 0.595 | neutral | None | None | None | None | I |
| P/W | 0.8305 | likely_pathogenic | 0.8402 | pathogenic | -0.986 | Destabilizing | 0.998 | D | 0.72 | deleterious | None | None | None | None | I |
| P/Y | 0.6496 | likely_pathogenic | 0.6497 | pathogenic | -0.71 | Destabilizing | 0.991 | D | 0.755 | deleterious | None | None | None | None | I |
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.