Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
| N2AB | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
| N2A | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
| N2B | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
| Novex-1 | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
| Novex-2 | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
| Novex-3 | 54 | 385;386;387 | chr2:178802273;178802272;178802271 | chr2:179667000;179666999;179666998 |
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/L | None | None | 0.094 | N | 0.469 | 0.26 | 0.378322506985 | gnomAD-4.0.0 | 4.10442E-06 | None | None | None | -1.127(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39576E-06 | 0 | 0 |
| V/M | rs139517732  |
-0.932 | 0.662 | N | 0.517 | 0.39 | None | gnomAD-2.1.1 | 4.25E-05 | None | None | None | -1.137(TCAP) | N | None | 0 | 2.82E-05 | None | 0 | 5.52597E-04 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs139517732 |
-0.932 | 0.662 | N | 0.517 | 0.39 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | -1.137(TCAP) | N | None | 0 | 6.54E-05 | 0 | 0 | 9.63391E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs139517732 |
-0.932 | 0.662 | N | 0.517 | 0.39 | None | 1000 genomes | 5.99042E-04 | None | None | None | -1.137(TCAP) | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| V/M | rs139517732 |
-0.932 | 0.662 | N | 0.517 | 0.39 | None |
Itoh-Satoh (2002)
Kumar (2016)
| None |
DCM 
|
het | None | -1.137(TCAP) | N | Genetic analysis of JP DCM families, unknown penetrance; decreases binding of TTN to TCAP (Y2H assay); Variant prioritisation; filtering with pathogenicity/stability tools; MD analysis of binding of TTN to TCAP | None | None | None | None | None | None | None | None | None | None | None |
| V/M | rs139517732 |
-0.932 | 0.662 | N | 0.517 | 0.39 | None | gnomAD-4.0.0 | 3.71722E-05 | None | None | None | -1.137(TCAP) | N | None | 1.33284E-05 | 3.33178E-05 | None | 0 | 1.11458E-03 | None | 0 | 1.65017E-04 | 3.38981E-06 | 0 | 3.19969E-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 | 0.4877 | ambiguous | 0.6859 | pathogenic | -1.902 | Destabilizing | 0.047 | N | 0.416 | neutral | N | 0.511093849 | None | -0.726(TCAP) | N |
| V/C | 0.9406 | likely_pathogenic | 0.9541 | pathogenic | -1.567 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | -1.103(TCAP) | N |
| V/D | 0.946 | likely_pathogenic | 0.9838 | pathogenic | -2.08 | Highly Destabilizing | 0.988 | D | 0.764 | deleterious | None | None | None | -0.647(TCAP) | N |
| V/E | 0.8698 | likely_pathogenic | 0.9455 | pathogenic | -1.946 | Destabilizing | 0.913 | D | 0.677 | prob.neutral | N | 0.5147763 | None | -0.808(TCAP) | N |
| V/F | 0.3646 | ambiguous | 0.5565 | ambiguous | -1.182 | Destabilizing | 0.969 | D | 0.703 | prob.neutral | None | None | None | -1.011(TCAP) | N |
| V/G | 0.6593 | likely_pathogenic | 0.8272 | pathogenic | -2.37 | Highly Destabilizing | 0.956 | D | 0.713 | prob.delet. | N | 0.516941769 | None | -0.602(TCAP) | N |
| V/H | 0.9613 | likely_pathogenic | 0.9861 | pathogenic | -2.061 | Highly Destabilizing | 0.998 | D | 0.764 | deleterious | None | None | None | -0.213(TCAP) | N |
| V/I | 0.0853 | likely_benign | 0.0974 | benign | -0.649 | Destabilizing | 0.01 | N | 0.328 | neutral | None | None | None | -1.127(TCAP) | N |
| V/K | 0.9331 | likely_pathogenic | 0.973 | pathogenic | -1.761 | Destabilizing | 0.937 | D | 0.667 | neutral | None | None | None | -1.235(TCAP) | N |
| V/L | 0.354 | ambiguous | 0.5092 | ambiguous | -0.649 | Destabilizing | 0.094 | N | 0.469 | neutral | N | 0.493178448 | None | -1.127(TCAP) | N |
| V/M | 0.2615 | likely_benign | 0.3965 | ambiguous | -0.676 | Destabilizing | 0.662 | D | 0.517 | neutral | N | 0.516807186 | None | -1.137(TCAP) | N |
| V/N | 0.8747 | likely_pathogenic | 0.9498 | pathogenic | -1.818 | Destabilizing | 0.818 | D | 0.777 | deleterious | None | None | None | -0.902(TCAP) | N |
| V/P | 0.9718 | likely_pathogenic | 0.99 | pathogenic | -1.035 | Destabilizing | 0.818 | D | 0.701 | prob.neutral | None | None | None | -0.99(TCAP) | N |
| V/Q | 0.8666 | likely_pathogenic | 0.9413 | pathogenic | -1.782 | Destabilizing | 0.955 | D | 0.703 | prob.neutral | None | None | None | -0.992(TCAP) | N |
| V/R | 0.9049 | likely_pathogenic | 0.961 | pathogenic | -1.449 | Destabilizing | 0.969 | D | 0.771 | deleterious | None | None | None | -1.094(TCAP) | N |
| V/S | 0.6909 | likely_pathogenic | 0.848 | pathogenic | -2.435 | Highly Destabilizing | 0.71 | D | 0.649 | neutral | None | None | None | -0.636(TCAP) | N |
| V/T | 0.5179 | ambiguous | 0.6778 | pathogenic | -2.166 | Highly Destabilizing | 0.663 | D | 0.605 | neutral | None | None | None | -0.817(TCAP) | N |
| V/W | 0.9645 | likely_pathogenic | 0.9878 | pathogenic | -1.568 | Destabilizing | 0.999 | D | 0.75 | deleterious | None | None | None | -1.219(TCAP) | N |
| V/Y | 0.8852 | likely_pathogenic | 0.9465 | pathogenic | -1.224 | Destabilizing | 0.985 | D | 0.691 | prob.neutral | None | None | None | -1.053(TCAP) | 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.