Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14601 | 44026;44027;44028 | chr2:178631247;178631246;178631245 | chr2:179495974;179495973;179495972 |
| N2AB | 12960 | 39103;39104;39105 | chr2:178631247;178631246;178631245 | chr2:179495974;179495973;179495972 |
| N2A | 12033 | 36322;36323;36324 | chr2:178631247;178631246;178631245 | chr2:179495974;179495973;179495972 |
| N2B | 5536 | 16831;16832;16833 | chr2:178631247;178631246;178631245 | chr2:179495974;179495973;179495972 |
| Novex-1 | 5661 | 17206;17207;17208 | chr2:178631247;178631246;178631245 | chr2:179495974;179495973;179495972 |
| Novex-2 | 5728 | 17407;17408;17409 | chr2:178631247;178631246;178631245 | chr2:179495974;179495973;179495972 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs748236664  |
-0.259 | 0.002 | N | 0.282 | 0.032 | 0.0482279557977 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| D/E | rs748236664 |
-0.259 | 0.002 | N | 0.282 | 0.032 | 0.0482279557977 | gnomAD-4.0.0 | 1.59455E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2407 | likely_benign | 0.4458 | ambiguous | -0.388 | Destabilizing | 0.201 | N | 0.501 | neutral | N | 0.48674289 | None | None | N |
| D/C | 0.8184 | likely_pathogenic | 0.9314 | pathogenic | -0.004 | Destabilizing | 0.982 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/E | 0.1709 | likely_benign | 0.3889 | ambiguous | -0.419 | Destabilizing | 0.002 | N | 0.282 | neutral | N | 0.441759814 | None | None | N |
| D/F | 0.7914 | likely_pathogenic | 0.9134 | pathogenic | -0.341 | Destabilizing | 0.947 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/G | 0.182 | likely_benign | 0.3221 | benign | -0.606 | Destabilizing | 0.201 | N | 0.5 | neutral | N | 0.445057166 | None | None | N |
| D/H | 0.4481 | ambiguous | 0.7266 | pathogenic | -0.337 | Destabilizing | 0.931 | D | 0.574 | neutral | D | 0.527295907 | None | None | N |
| D/I | 0.6334 | likely_pathogenic | 0.8566 | pathogenic | 0.145 | Stabilizing | 0.826 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/K | 0.4516 | ambiguous | 0.7551 | pathogenic | 0.162 | Stabilizing | 0.25 | N | 0.523 | neutral | None | None | None | None | N |
| D/L | 0.6122 | likely_pathogenic | 0.826 | pathogenic | 0.145 | Stabilizing | 0.7 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/M | 0.7574 | likely_pathogenic | 0.9072 | pathogenic | 0.37 | Stabilizing | 0.982 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/N | 0.116 | likely_benign | 0.2345 | benign | -0.134 | Destabilizing | 0.201 | N | 0.501 | neutral | N | 0.450304995 | None | None | N |
| D/P | 0.948 | likely_pathogenic | 0.9835 | pathogenic | -0.01 | Destabilizing | 0.826 | D | 0.579 | neutral | None | None | None | None | N |
| D/Q | 0.4183 | ambiguous | 0.7173 | pathogenic | -0.101 | Destabilizing | 0.539 | D | 0.551 | neutral | None | None | None | None | N |
| D/R | 0.5176 | ambiguous | 0.7973 | pathogenic | 0.289 | Stabilizing | 0.539 | D | 0.651 | neutral | None | None | None | None | N |
| D/S | 0.167 | likely_benign | 0.3236 | benign | -0.255 | Destabilizing | 0.02 | N | 0.284 | neutral | None | None | None | None | N |
| D/T | 0.3517 | ambiguous | 0.6201 | pathogenic | -0.087 | Destabilizing | 0.25 | N | 0.521 | neutral | None | None | None | None | N |
| D/V | 0.4007 | ambiguous | 0.6387 | pathogenic | -0.01 | Destabilizing | 0.638 | D | 0.707 | prob.neutral | D | 0.665812278 | None | None | N |
| D/W | 0.941 | likely_pathogenic | 0.9754 | pathogenic | -0.208 | Destabilizing | 0.982 | D | 0.718 | prob.delet. | None | None | None | None | N |
| D/Y | 0.3364 | likely_benign | 0.5339 | ambiguous | -0.11 | Destabilizing | 0.976 | D | 0.709 | prob.delet. | D | 0.574874143 | 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.