Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15794 | 47605;47606;47607 | chr2:178617971;178617970;178617969 | chr2:179482698;179482697;179482696 |
| N2AB | 14153 | 42682;42683;42684 | chr2:178617971;178617970;178617969 | chr2:179482698;179482697;179482696 |
| N2A | 13226 | 39901;39902;39903 | chr2:178617971;178617970;178617969 | chr2:179482698;179482697;179482696 |
| N2B | 6729 | 20410;20411;20412 | chr2:178617971;178617970;178617969 | chr2:179482698;179482697;179482696 |
| Novex-1 | 6854 | 20785;20786;20787 | chr2:178617971;178617970;178617969 | chr2:179482698;179482697;179482696 |
| Novex-2 | 6921 | 20986;20987;20988 | chr2:178617971;178617970;178617969 | chr2:179482698;179482697;179482696 |
| 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/I | rs727504878  |
-0.73 | 0.002 | N | 0.275 | 0.033 | 0.178374595973 | gnomAD-2.1.1 | 1.08791E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 8.82468E-04 | None | 0 | 0 | 0 |
| V/I | rs727504878 |
-0.73 | 0.002 | N | 0.275 | 0.033 | 0.178374595973 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 1.95313E-04 | None | 0 | 0 | 0 | 8.29531E-04 | 0 |
| V/I | rs727504878 |
-0.73 | 0.002 | N | 0.275 | 0.033 | 0.178374595973 | gnomAD-4.0.0 | 6.4498E-05 | None | None | None | None | N | None | 1.33733E-05 | 0 | None | 0 | 1.11837E-04 | None | 0 | 0 | 5.93671E-06 | 9.88424E-04 | 1.60287E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3539 | ambiguous | 0.3439 | ambiguous | -2.217 | Highly Destabilizing | 0.104 | N | 0.586 | neutral | N | 0.494765299 | None | None | N |
| V/C | 0.7112 | likely_pathogenic | 0.6674 | pathogenic | -1.865 | Destabilizing | 0.968 | D | 0.696 | prob.neutral | None | None | None | None | N |
| V/D | 0.5749 | likely_pathogenic | 0.574 | pathogenic | -3.117 | Highly Destabilizing | 0.667 | D | 0.76 | deleterious | N | 0.504735819 | None | None | N |
| V/E | 0.4007 | ambiguous | 0.4018 | ambiguous | -2.957 | Highly Destabilizing | 0.726 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/F | 0.2206 | likely_benign | 0.1986 | benign | -1.328 | Destabilizing | 0.715 | D | 0.679 | prob.neutral | N | 0.475777038 | None | None | N |
| V/G | 0.5004 | ambiguous | 0.4912 | ambiguous | -2.671 | Highly Destabilizing | 0.667 | D | 0.722 | prob.delet. | D | 0.577290922 | None | None | N |
| V/H | 0.5884 | likely_pathogenic | 0.5642 | pathogenic | -2.329 | Highly Destabilizing | 0.968 | D | 0.753 | deleterious | None | None | None | None | N |
| V/I | 0.0627 | likely_benign | 0.0617 | benign | -0.965 | Destabilizing | 0.002 | N | 0.275 | neutral | N | 0.430111118 | None | None | N |
| V/K | 0.5143 | ambiguous | 0.5316 | ambiguous | -1.934 | Destabilizing | 0.726 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/L | 0.171 | likely_benign | 0.1583 | benign | -0.965 | Destabilizing | 0.022 | N | 0.44 | neutral | N | 0.477795921 | None | None | N |
| V/M | 0.1587 | likely_benign | 0.1501 | benign | -1.077 | Destabilizing | 0.567 | D | 0.648 | neutral | None | None | None | None | N |
| V/N | 0.3685 | ambiguous | 0.357 | ambiguous | -2.168 | Highly Destabilizing | 0.89 | D | 0.773 | deleterious | None | None | None | None | N |
| V/P | 0.9798 | likely_pathogenic | 0.9795 | pathogenic | -1.357 | Destabilizing | 0.89 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/Q | 0.4004 | ambiguous | 0.3961 | ambiguous | -2.116 | Highly Destabilizing | 0.89 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/R | 0.4294 | ambiguous | 0.4438 | ambiguous | -1.588 | Destabilizing | 0.726 | D | 0.773 | deleterious | None | None | None | None | N |
| V/S | 0.3683 | ambiguous | 0.3495 | ambiguous | -2.676 | Highly Destabilizing | 0.726 | D | 0.651 | neutral | None | None | None | None | N |
| V/T | 0.2451 | likely_benign | 0.2365 | benign | -2.402 | Highly Destabilizing | 0.272 | N | 0.59 | neutral | None | None | None | None | N |
| V/W | 0.8311 | likely_pathogenic | 0.813 | pathogenic | -1.82 | Destabilizing | 0.968 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/Y | 0.564 | ambiguous | 0.5383 | ambiguous | -1.514 | Destabilizing | 0.726 | D | 0.703 | prob.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.