Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29416 | 88471;88472;88473 | chr2:178556908;178556907;178556906 | chr2:179421635;179421634;179421633 |
| N2AB | 27775 | 83548;83549;83550 | chr2:178556908;178556907;178556906 | chr2:179421635;179421634;179421633 |
| N2A | 26848 | 80767;80768;80769 | chr2:178556908;178556907;178556906 | chr2:179421635;179421634;179421633 |
| N2B | 20351 | 61276;61277;61278 | chr2:178556908;178556907;178556906 | chr2:179421635;179421634;179421633 |
| Novex-1 | 20476 | 61651;61652;61653 | chr2:178556908;178556907;178556906 | chr2:179421635;179421634;179421633 |
| Novex-2 | 20543 | 61852;61853;61854 | chr2:178556908;178556907;178556906 | chr2:179421635;179421634;179421633 |
| 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/A | None | None | 0.008 | N | 0.295 | 0.181 | 0.350524144436 | gnomAD-4.0.0 | 1.59134E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| V/F | rs755325663  |
-0.578 | 0.901 | N | 0.564 | 0.305 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | I | None | 2.47954E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs755325663 |
-0.578 | 0.901 | N | 0.564 | 0.305 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | I | None | 2.65418E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | rs755325663 |
-0.578 | 0.901 | N | 0.564 | 0.305 | None | gnomAD-4.0.0 | 1.36334E-05 | None | None | None | None | I | None | 2.66951E-04 | 1.66694E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60102E-05 |
| V/I | None | None | 0.008 | N | 0.237 | 0.068 | 0.249502417897 | gnomAD-4.0.0 | 6.84223E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1775 | likely_benign | 0.124 | benign | -0.227 | Destabilizing | 0.008 | N | 0.295 | neutral | N | 0.373371739 | None | None | I |
| V/C | 0.8387 | likely_pathogenic | 0.7901 | pathogenic | -0.706 | Destabilizing | 0.989 | D | 0.568 | neutral | None | None | None | None | I |
| V/D | 0.8295 | likely_pathogenic | 0.6956 | pathogenic | -0.021 | Destabilizing | 0.949 | D | 0.699 | prob.neutral | N | 0.467659028 | None | None | I |
| V/E | 0.763 | likely_pathogenic | 0.6377 | pathogenic | -0.14 | Destabilizing | 0.923 | D | 0.657 | neutral | None | None | None | None | I |
| V/F | 0.3766 | ambiguous | 0.2653 | benign | -0.618 | Destabilizing | 0.901 | D | 0.564 | neutral | N | 0.509843463 | None | None | I |
| V/G | 0.4057 | ambiguous | 0.2966 | benign | -0.281 | Destabilizing | 0.82 | D | 0.616 | neutral | N | 0.503645422 | None | None | I |
| V/H | 0.8872 | likely_pathogenic | 0.7914 | pathogenic | 0.014 | Stabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/I | 0.1061 | likely_benign | 0.0852 | benign | -0.234 | Destabilizing | 0.008 | N | 0.237 | neutral | N | 0.447658853 | None | None | I |
| V/K | 0.8289 | likely_pathogenic | 0.7475 | pathogenic | -0.146 | Destabilizing | 0.923 | D | 0.659 | neutral | None | None | None | None | I |
| V/L | 0.4096 | ambiguous | 0.2858 | benign | -0.234 | Destabilizing | 0.156 | N | 0.479 | neutral | N | 0.486427885 | None | None | I |
| V/M | 0.2844 | likely_benign | 0.1947 | benign | -0.334 | Destabilizing | 0.923 | D | 0.485 | neutral | None | None | None | None | I |
| V/N | 0.6175 | likely_pathogenic | 0.4296 | ambiguous | -0.018 | Destabilizing | 0.961 | D | 0.701 | prob.neutral | None | None | None | None | I |
| V/P | 0.8801 | likely_pathogenic | 0.775 | pathogenic | -0.203 | Destabilizing | 0.961 | D | 0.669 | neutral | None | None | None | None | I |
| V/Q | 0.7226 | likely_pathogenic | 0.5877 | pathogenic | -0.217 | Destabilizing | 0.961 | D | 0.668 | neutral | None | None | None | None | I |
| V/R | 0.7451 | likely_pathogenic | 0.6337 | pathogenic | 0.237 | Stabilizing | 0.961 | D | 0.702 | prob.neutral | None | None | None | None | I |
| V/S | 0.335 | likely_benign | 0.2274 | benign | -0.349 | Destabilizing | 0.858 | D | 0.577 | neutral | None | None | None | None | I |
| V/T | 0.2795 | likely_benign | 0.1986 | benign | -0.372 | Destabilizing | 0.775 | D | 0.487 | neutral | None | None | None | None | I |
| V/W | 0.9602 | likely_pathogenic | 0.9188 | pathogenic | -0.688 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | I |
| V/Y | 0.8583 | likely_pathogenic | 0.7638 | pathogenic | -0.384 | Destabilizing | 0.961 | D | 0.558 | neutral | 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.