Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
| N2AB | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
| N2A | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
| N2B | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
| Novex-1 | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
| Novex-2 | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
| Novex-3 | 178 | 757;758;759 | chr2:178800446;178800445;178800444 | chr2:179665173;179665172;179665171 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | -3.04 | 0.993 | D | 0.571 | 0.833 | 0.844504697091 |
Hastings (2016) 
Jiang (2021)
| None |
DCM 
LVNC
|
het | None | -1.921(TCAP) | N | Linkage analysis in single 3-generation DCM family, co-segregates with condition (n = 8, 8 affected (14 total)); features of LVNC; domain destabilisation and impaired TCAP binding in vitro; knock-in mice mutant show phenotype under challenge conditions | None | None | None | None | None | None | None | None | None | None | None |
| A/S | None | None | 0.999 | D | 0.585 | 0.582 | 0.585593966701 | gnomAD-4.0.0 | 1.59045E-06 | None | None | None | -1.174(TCAP) | N | None | 0 | 2.28624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs1304644881 |
None | 1.0 | D | 0.691 | 0.591 | 0.704534750623 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.295(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| A/V | rs1304644881 |
None | 1.0 | D | 0.691 | 0.591 | 0.704534750623 | gnomAD-4.0.0 | 8.05436E-06 | None | None | None | -1.295(TCAP) | N | None | 0 | 0 | None | 1.01338E-04 | 0 | None | 0 | 1.64366E-04 | 5.08467E-06 | 2.19587E-05 | 1.60036E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.9308 | likely_pathogenic | 0.9419 | pathogenic | -1.567 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | -1.745(TCAP) | N |
| A/D | 0.9987 | likely_pathogenic | 0.9987 | pathogenic | -2.864 | Highly Destabilizing | 0.993 | D | 0.571 | neutral | D | 0.849193772 | None | -1.921(TCAP) | N |
| A/E | 0.9966 | likely_pathogenic | 0.9967 | pathogenic | -2.695 | Highly Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | -2.122(TCAP) | N |
| A/F | 0.984 | likely_pathogenic | 0.9826 | pathogenic | -0.855 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | -1.196(TCAP) | N |
| A/G | 0.6927 | likely_pathogenic | 0.7361 | pathogenic | -1.835 | Destabilizing | 0.985 | D | 0.598 | neutral | D | 0.781844336 | None | -0.817(TCAP) | N |
| A/H | 0.9983 | likely_pathogenic | 0.9983 | pathogenic | -2.049 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | -0.855(TCAP) | N |
| A/I | 0.8862 | likely_pathogenic | 0.8994 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | -1.468(TCAP) | N |
| A/K | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -1.484 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | -2.193(TCAP) | N |
| A/L | 0.8488 | likely_pathogenic | 0.8538 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | -1.468(TCAP) | N |
| A/M | 0.9518 | likely_pathogenic | 0.954 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | -1.542(TCAP) | N |
| A/N | 0.9973 | likely_pathogenic | 0.9974 | pathogenic | -1.774 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | -1.547(TCAP) | N |
| A/P | 0.9973 | likely_pathogenic | 0.9975 | pathogenic | -0.628 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.849839023 | None | -1.295(TCAP) | N |
| A/Q | 0.9943 | likely_pathogenic | 0.9943 | pathogenic | -1.642 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | -1.715(TCAP) | N |
| A/R | 0.9953 | likely_pathogenic | 0.9954 | pathogenic | -1.437 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | -2.282(TCAP) | N |
| A/S | 0.6512 | likely_pathogenic | 0.67 | pathogenic | -2.121 | Highly Destabilizing | 0.999 | D | 0.585 | neutral | D | 0.752369831 | None | -1.174(TCAP) | N |
| A/T | 0.7858 | likely_pathogenic | 0.8089 | pathogenic | -1.849 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | D | 0.782520912 | None | -1.396(TCAP) | N |
| A/V | 0.6135 | likely_pathogenic | 0.6429 | pathogenic | -0.628 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.638714974 | None | -1.295(TCAP) | N |
| A/W | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -1.563 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | -1.415(TCAP) | N |
| A/Y | 0.9957 | likely_pathogenic | 0.9957 | pathogenic | -1.112 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | -1.176(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.