Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34072 | 102439;102440;102441 | chr2:178534401;178534400;178534399 | chr2:179399128;179399127;179399126 |
| N2AB | 32431 | 97516;97517;97518 | chr2:178534401;178534400;178534399 | chr2:179399128;179399127;179399126 |
| N2A | 31504 | 94735;94736;94737 | chr2:178534401;178534400;178534399 | chr2:179399128;179399127;179399126 |
| N2B | 25007 | 75244;75245;75246 | chr2:178534401;178534400;178534399 | chr2:179399128;179399127;179399126 |
| Novex-1 | 25132 | 75619;75620;75621 | chr2:178534401;178534400;178534399 | chr2:179399128;179399127;179399126 |
| Novex-2 | 25199 | 75820;75821;75822 | chr2:178534401;178534400;178534399 | chr2:179399128;179399127;179399126 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
- RefSeq wild type amino acid: W
- RefSeq wild type transcript codon: TGG
- RefSeq wild type template codon: ACC
- Domain: Kinase-1
- Domain position: 260
- Q(SASA): 0.1071
- Predicted PPI site: N
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/R | rs375159973  |
-2.479 | None | D | None | 0.829 | 0.779170189427 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| W/R | rs375159973 |
-2.479 | None | D | None | 0.829 | 0.779170189427 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| W/R | rs375159973 |
-2.479 | None | D | None | 0.829 | 0.779170189427 |
Chauveau (2013)
Rees (2021)
| None |
CM
MmD-HD
|
comp het with E2989Efs*4 / comp het with R7796* | None | None | N | Genetic analysis of TTN in 30 CM patients; comp het with R7796*; Domain unfolded in vitro (Tm 17 degrees lower than WT); Also found by WES prioritisation in 23 families with congenital CM; comp het with E2989Efs*4; loss of interactions with protein binding partners (Y2H); recessive inheritance | None | None | None | None | None | None | None | None | None | None | None |
| W/R | rs375159973 |
-2.479 | None | D | None | 0.829 | 0.779170189427 | gnomAD-4.0.0 | 2.17264E-05 | None | None | None | None | N | None | 0 | 1.66683E-05 | None | 0 | 2.22866E-05 | None | 0 | 0 | 2.62758E-05 | 1.09789E-05 | 1.60138E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9331 | likely_pathogenic | 0.9018 | pathogenic | -3.169 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/C | 0.9847 | likely_pathogenic | 0.9775 | pathogenic | -1.827 | Destabilizing | None | None | None | None | D | 0.554114239 | None | None | N |
| W/D | 0.9874 | likely_pathogenic | 0.9772 | pathogenic | -3.705 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/E | 0.9888 | likely_pathogenic | 0.9799 | pathogenic | -3.592 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/F | 0.4121 | ambiguous | 0.3659 | ambiguous | -2.163 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/G | 0.9243 | likely_pathogenic | 0.8871 | pathogenic | -3.394 | Highly Destabilizing | None | None | None | None | D | 0.55386075 | None | None | N |
| W/H | 0.9536 | likely_pathogenic | 0.9313 | pathogenic | -2.832 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/I | 0.9286 | likely_pathogenic | 0.9016 | pathogenic | -2.29 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/K | 0.9953 | likely_pathogenic | 0.9903 | pathogenic | -2.784 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/L | 0.7463 | likely_pathogenic | 0.6953 | pathogenic | -2.29 | Highly Destabilizing | None | None | None | None | D | 0.532207642 | None | None | N |
| W/M | 0.9506 | likely_pathogenic | 0.9328 | pathogenic | -1.801 | Destabilizing | None | None | None | None | None | None | None | None | N |
| W/N | 0.9873 | likely_pathogenic | 0.9784 | pathogenic | -3.483 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/P | 0.9933 | likely_pathogenic | 0.9916 | pathogenic | -2.613 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/Q | 0.9938 | likely_pathogenic | 0.989 | pathogenic | -3.28 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/R | 0.9898 | likely_pathogenic | 0.9826 | pathogenic | -2.649 | Highly Destabilizing | None | None | None | None | D | 0.55386075 | None | None | N |
| W/S | 0.9109 | likely_pathogenic | 0.8631 | pathogenic | -3.53 | Highly Destabilizing | None | None | None | None | D | 0.553353771 | None | None | N |
| W/T | 0.9555 | likely_pathogenic | 0.9366 | pathogenic | -3.338 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/V | 0.9068 | likely_pathogenic | 0.8748 | pathogenic | -2.613 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| W/Y | 0.717 | likely_pathogenic | 0.6503 | pathogenic | -2.11 | Highly Destabilizing | None | None | None | None | 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.