Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23414 | 70465;70466;70467 | chr2:178575892;178575891;178575890 | chr2:179440619;179440618;179440617 |
| N2AB | 21773 | 65542;65543;65544 | chr2:178575892;178575891;178575890 | chr2:179440619;179440618;179440617 |
| N2A | 20846 | 62761;62762;62763 | chr2:178575892;178575891;178575890 | chr2:179440619;179440618;179440617 |
| N2B | 14349 | 43270;43271;43272 | chr2:178575892;178575891;178575890 | chr2:179440619;179440618;179440617 |
| Novex-1 | 14474 | 43645;43646;43647 | chr2:178575892;178575891;178575890 | chr2:179440619;179440618;179440617 |
| Novex-2 | 14541 | 43846;43847;43848 | chr2:178575892;178575891;178575890 | chr2:179440619;179440618;179440617 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs759158138  |
-1.226 | 0.772 | N | 0.545 | 0.196 | 0.515430650102 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| V/F | rs759158138 |
-1.226 | 0.772 | N | 0.545 | 0.196 | 0.515430650102 | gnomAD-4.0.0 | 4.77493E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.578E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2149 | likely_benign | 0.2439 | benign | -1.665 | Destabilizing | 0.001 | N | 0.171 | neutral | N | 0.495804225 | None | None | N |
| V/C | 0.6212 | likely_pathogenic | 0.6454 | pathogenic | -1.361 | Destabilizing | 0.972 | D | 0.532 | neutral | None | None | None | None | N |
| V/D | 0.4117 | ambiguous | 0.4844 | ambiguous | -1.59 | Destabilizing | 0.326 | N | 0.573 | neutral | N | 0.453130883 | None | None | N |
| V/E | 0.2718 | likely_benign | 0.324 | benign | -1.438 | Destabilizing | 0.561 | D | 0.551 | neutral | None | None | None | None | N |
| V/F | 0.1861 | likely_benign | 0.2014 | benign | -1.003 | Destabilizing | 0.772 | D | 0.545 | neutral | N | 0.462426837 | None | None | N |
| V/G | 0.3395 | likely_benign | 0.3661 | ambiguous | -2.135 | Highly Destabilizing | 0.166 | N | 0.517 | neutral | N | 0.477911898 | None | None | N |
| V/H | 0.4606 | ambiguous | 0.511 | ambiguous | -1.789 | Destabilizing | 0.009 | N | 0.499 | neutral | None | None | None | None | N |
| V/I | 0.073 | likely_benign | 0.071 | benign | -0.403 | Destabilizing | 0.166 | N | 0.447 | neutral | N | 0.436294562 | None | None | N |
| V/K | 0.4378 | ambiguous | 0.4857 | ambiguous | -1.211 | Destabilizing | 0.561 | D | 0.545 | neutral | None | None | None | None | N |
| V/L | 0.1612 | likely_benign | 0.1628 | benign | -0.403 | Destabilizing | 0.001 | N | 0.191 | neutral | N | 0.480200054 | None | None | N |
| V/M | 0.1194 | likely_benign | 0.1176 | benign | -0.552 | Destabilizing | 0.818 | D | 0.538 | neutral | None | None | None | None | N |
| V/N | 0.2235 | likely_benign | 0.254 | benign | -1.332 | Destabilizing | 0.017 | N | 0.489 | neutral | None | None | None | None | N |
| V/P | 0.9542 | likely_pathogenic | 0.9574 | pathogenic | -0.792 | Destabilizing | 0.901 | D | 0.591 | neutral | None | None | None | None | N |
| V/Q | 0.2827 | likely_benign | 0.3191 | benign | -1.265 | Destabilizing | 0.901 | D | 0.589 | neutral | None | None | None | None | N |
| V/R | 0.3993 | ambiguous | 0.4382 | ambiguous | -1.034 | Destabilizing | 0.561 | D | 0.612 | neutral | None | None | None | None | N |
| V/S | 0.1838 | likely_benign | 0.2148 | benign | -2.021 | Highly Destabilizing | 0.209 | N | 0.487 | neutral | None | None | None | None | N |
| V/T | 0.1351 | likely_benign | 0.1512 | benign | -1.728 | Destabilizing | 0.007 | N | 0.177 | neutral | None | None | None | None | N |
| V/W | 0.8246 | likely_pathogenic | 0.8424 | pathogenic | -1.369 | Destabilizing | 0.991 | D | 0.633 | neutral | None | None | None | None | N |
| V/Y | 0.5063 | ambiguous | 0.5362 | ambiguous | -0.982 | Destabilizing | 0.818 | D | 0.547 | 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.