Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33903 | 101932;101933;101934 | chr2:178534908;178534907;178534906 | chr2:179399635;179399634;179399633 |
| N2AB | 32262 | 97009;97010;97011 | chr2:178534908;178534907;178534906 | chr2:179399635;179399634;179399633 |
| N2A | 31335 | 94228;94229;94230 | chr2:178534908;178534907;178534906 | chr2:179399635;179399634;179399633 |
| N2B | 24838 | 74737;74738;74739 | chr2:178534908;178534907;178534906 | chr2:179399635;179399634;179399633 |
| Novex-1 | 24963 | 75112;75113;75114 | chr2:178534908;178534907;178534906 | chr2:179399635;179399634;179399633 |
| Novex-2 | 25030 | 75313;75314;75315 | chr2:178534908;178534907;178534906 | chr2:179399635;179399634;179399633 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
- RefSeq wild type amino acid: R
- RefSeq wild type transcript codon: CGC
- RefSeq wild type template codon: GCG
- Domain: Kinase-1
- Domain position: 91
- Q(SASA): 0.0939
- 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs772574722  |
-2.078 | None | N | None | 0.403 | 0.754502143824 | gnomAD-2.1.1 | 4.69E-05 | None | None | None | None | N | None | 1.24131E-04 | 2.83E-05 | None | 0 | 5.13E-05 | None | 6.54E-05 | None | 0 | 3.91E-05 | 1.41283E-04 |
| R/C | rs772574722 |
-2.078 | None | N | None | 0.403 | 0.754502143824 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 7.24E-05 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs772574722 |
-2.078 | None | N | None | 0.403 | 0.754502143824 | gnomAD-4.0.0 | 2.60895E-05 | None | None | None | None | N | None | 4.00566E-05 | 8.335E-05 | None | 0 | 2.22816E-05 | None | 0 | 0 | 2.45809E-05 | 2.19578E-05 | 3.20328E-05 |
| R/H | rs72629782 |
-2.243 | None | N | None | 0.447 | None | gnomAD-2.1.1 | 2.41827E-04 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 1.99979E-03 | None | 3.27E-05 | None | 7.63839E-04 | 6.26E-05 | 0 |
| R/H | rs72629782 |
-2.243 | None | N | None | 0.447 | None | gnomAD-3.1.2 | 1.90576E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92382E-03 | None | 1.41429E-03 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs72629782 |
-2.243 | None | N | None | 0.447 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| R/H | rs72629782 |
-2.243 | None | N | None | 0.447 | None |
Huang (2021)
| None |
Other
|
comp het with T2014A (in cis), c.1800+1G>A (in trans) | None | None | N | Genetic analysis of NMD patients; variant prioritisation; no validation | None | None | None | None | None | None | None | None | None | None | None |
| R/H | rs72629782 |
-2.243 | None | N | None | 0.447 | None | gnomAD-4.0.0 | 9.25565E-05 | None | None | None | None | N | None | 3.99808E-05 | 0 | None | 0 | 1.09204E-03 | None | 7.82838E-04 | 1.65017E-04 | 3.64475E-05 | 1.09803E-05 | 8.00512E-05 |
| R/L | rs72629782 |
None | None | N | None | 0.489 | 0.684638531588 | gnomAD-4.0.0 | 1.37218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79896E-06 | 0 | 0 |
| R/S | None | None | None | N | None | 0.39 | 0.547470054201 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/S | None | None | None | N | None | 0.39 | 0.547470054201 | gnomAD-4.0.0 | 2.48471E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39047E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8749 | likely_pathogenic | 0.8612 | pathogenic | -2.295 | Highly Destabilizing | None | None | None | None | None | None | None | None | N |
| R/C | 0.7067 | likely_pathogenic | 0.6083 | pathogenic | -2.105 | Highly Destabilizing | None | None | None | None | N | 0.51870338 | None | None | N |
| R/D | 0.939 | likely_pathogenic | 0.932 | pathogenic | -0.895 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/E | 0.7724 | likely_pathogenic | 0.7359 | pathogenic | -0.671 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/F | 0.9559 | likely_pathogenic | 0.9396 | pathogenic | -1.658 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/G | 0.7916 | likely_pathogenic | 0.7555 | pathogenic | -2.639 | Highly Destabilizing | None | None | None | None | N | 0.514489639 | None | None | N |
| R/H | 0.442 | ambiguous | 0.3726 | ambiguous | -2.31 | Highly Destabilizing | None | None | None | None | N | 0.459463076 | None | None | N |
| R/I | 0.8061 | likely_pathogenic | 0.764 | pathogenic | -1.289 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/K | 0.3272 | likely_benign | 0.275 | benign | -1.193 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/L | 0.7441 | likely_pathogenic | 0.686 | pathogenic | -1.289 | Destabilizing | None | None | None | None | N | 0.446915066 | None | None | N |
| R/M | 0.8163 | likely_pathogenic | 0.7444 | pathogenic | -1.702 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/N | 0.893 | likely_pathogenic | 0.885 | pathogenic | -1.255 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/P | 0.9802 | likely_pathogenic | 0.9769 | pathogenic | -1.615 | Destabilizing | None | None | None | None | N | 0.499718434 | None | None | N |
| R/Q | 0.3684 | ambiguous | 0.2977 | benign | -1.209 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/S | 0.9221 | likely_pathogenic | 0.9098 | pathogenic | -2.329 | Highly Destabilizing | None | None | None | None | N | 0.491612779 | None | None | N |
| R/T | 0.8256 | likely_pathogenic | 0.7992 | pathogenic | -1.878 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/V | 0.8602 | likely_pathogenic | 0.8215 | pathogenic | -1.615 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/W | 0.7518 | likely_pathogenic | 0.6528 | pathogenic | -1.06 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/Y | 0.8715 | likely_pathogenic | 0.8251 | pathogenic | -0.953 | 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.