Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26624 | 80095;80096;80097 | chr2:178566262;178566261;178566260 | chr2:179430989;179430988;179430987 |
| N2AB | 24983 | 75172;75173;75174 | chr2:178566262;178566261;178566260 | chr2:179430989;179430988;179430987 |
| N2A | 24056 | 72391;72392;72393 | chr2:178566262;178566261;178566260 | chr2:179430989;179430988;179430987 |
| N2B | 17559 | 52900;52901;52902 | chr2:178566262;178566261;178566260 | chr2:179430989;179430988;179430987 |
| Novex-1 | 17684 | 53275;53276;53277 | chr2:178566262;178566261;178566260 | chr2:179430989;179430988;179430987 |
| Novex-2 | 17751 | 53476;53477;53478 | chr2:178566262;178566261;178566260 | chr2:179430989;179430988;179430987 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs373540030  |
-2.455 | 0.994 | D | 0.846 | 0.709 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/N | rs373540030 |
-2.455 | 0.994 | D | 0.846 | 0.709 | None | gnomAD-4.0.0 | 4.78978E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11575E-05 | 0 |
| I/S | None | None | 0.983 | D | 0.837 | 0.72 | 0.914779128301 | gnomAD-4.0.0 | 6.84254E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73551E-04 | 0 | 0 | 0 |
| I/T | rs373540030 |
-2.757 | 0.892 | D | 0.786 | 0.642 | 0.799861211108 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 0 | 0 |
| I/T | rs373540030 |
-2.757 | 0.892 | D | 0.786 | 0.642 | 0.799861211108 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs373540030 |
-2.757 | 0.892 | D | 0.786 | 0.642 | 0.799861211108 | gnomAD-4.0.0 | 4.95808E-06 | None | None | None | None | N | None | 1.33522E-05 | 0 | None | 0 | 0 | None | 0 | 1.64528E-04 | 8.47677E-07 | 5.48944E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6318 | likely_pathogenic | 0.5373 | ambiguous | -2.406 | Highly Destabilizing | 0.845 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.7484 | likely_pathogenic | 0.7007 | pathogenic | -1.613 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/D | 0.9693 | likely_pathogenic | 0.957 | pathogenic | -2.501 | Highly Destabilizing | 0.996 | D | 0.85 | deleterious | None | None | None | None | N |
| I/E | 0.9321 | likely_pathogenic | 0.9068 | pathogenic | -2.299 | Highly Destabilizing | 0.987 | D | 0.852 | deleterious | None | None | None | None | N |
| I/F | 0.3705 | ambiguous | 0.3507 | ambiguous | -1.448 | Destabilizing | 0.967 | D | 0.727 | prob.delet. | N | 0.514328239 | None | None | N |
| I/G | 0.9112 | likely_pathogenic | 0.8721 | pathogenic | -2.935 | Highly Destabilizing | 0.987 | D | 0.85 | deleterious | None | None | None | None | N |
| I/H | 0.9127 | likely_pathogenic | 0.8911 | pathogenic | -2.314 | Highly Destabilizing | 0.999 | D | 0.841 | deleterious | None | None | None | None | N |
| I/K | 0.8544 | likely_pathogenic | 0.8032 | pathogenic | -1.884 | Destabilizing | 0.987 | D | 0.851 | deleterious | None | None | None | None | N |
| I/L | 0.2258 | likely_benign | 0.2075 | benign | -0.896 | Destabilizing | 0.426 | N | 0.457 | neutral | N | 0.503590591 | None | None | N |
| I/M | 0.148 | likely_benign | 0.1329 | benign | -0.752 | Destabilizing | 0.983 | D | 0.695 | prob.neutral | D | 0.531636027 | None | None | N |
| I/N | 0.7346 | likely_pathogenic | 0.6822 | pathogenic | -2.129 | Highly Destabilizing | 0.994 | D | 0.846 | deleterious | D | 0.550082677 | None | None | N |
| I/P | 0.9282 | likely_pathogenic | 0.9026 | pathogenic | -1.378 | Destabilizing | 0.996 | D | 0.842 | deleterious | None | None | None | None | N |
| I/Q | 0.8839 | likely_pathogenic | 0.8406 | pathogenic | -2.03 | Highly Destabilizing | 0.996 | D | 0.855 | deleterious | None | None | None | None | N |
| I/R | 0.8321 | likely_pathogenic | 0.7853 | pathogenic | -1.558 | Destabilizing | 0.987 | D | 0.854 | deleterious | None | None | None | None | N |
| I/S | 0.722 | likely_pathogenic | 0.6447 | pathogenic | -2.833 | Highly Destabilizing | 0.983 | D | 0.837 | deleterious | D | 0.523331141 | None | None | N |
| I/T | 0.6145 | likely_pathogenic | 0.5416 | ambiguous | -2.482 | Highly Destabilizing | 0.892 | D | 0.786 | deleterious | D | 0.531636027 | None | None | N |
| I/V | 0.0885 | likely_benign | 0.0845 | benign | -1.378 | Destabilizing | 0.011 | N | 0.189 | neutral | N | 0.436137925 | None | None | N |
| I/W | 0.926 | likely_pathogenic | 0.929 | pathogenic | -1.798 | Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| I/Y | 0.775 | likely_pathogenic | 0.7664 | pathogenic | -1.495 | Destabilizing | 0.987 | D | 0.746 | deleterious | 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.