Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18346 | 55261;55262;55263 | chr2:178602366;178602365;178602364 | chr2:179467093;179467092;179467091 |
| N2AB | 16705 | 50338;50339;50340 | chr2:178602366;178602365;178602364 | chr2:179467093;179467092;179467091 |
| N2A | 15778 | 47557;47558;47559 | chr2:178602366;178602365;178602364 | chr2:179467093;179467092;179467091 |
| N2B | 9281 | 28066;28067;28068 | chr2:178602366;178602365;178602364 | chr2:179467093;179467092;179467091 |
| Novex-1 | 9406 | 28441;28442;28443 | chr2:178602366;178602365;178602364 | chr2:179467093;179467092;179467091 |
| Novex-2 | 9473 | 28642;28643;28644 | chr2:178602366;178602365;178602364 | chr2:179467093;179467092;179467091 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs573136400  |
-1.236 | 0.781 | N | 0.775 | 0.302 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 3.72362E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/I | rs573136400 |
-1.236 | 0.781 | N | 0.775 | 0.302 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 2.41406E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs573136400 |
-1.236 | 0.781 | N | 0.775 | 0.302 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/I | rs573136400 |
-1.236 | 0.781 | N | 0.775 | 0.302 | None | gnomAD-4.0.0 | 1.24001E-05 | None | None | None | None | N | None | 2.26763E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09835E-05 | 3.20349E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5497 | ambiguous | 0.5725 | pathogenic | -1.695 | Destabilizing | 0.25 | N | 0.652 | neutral | None | None | None | None | N |
| R/C | 0.1573 | likely_benign | 0.1646 | benign | -1.676 | Destabilizing | 0.982 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/D | 0.8497 | likely_pathogenic | 0.8535 | pathogenic | -0.529 | Destabilizing | 0.7 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/E | 0.5749 | likely_pathogenic | 0.5757 | pathogenic | -0.346 | Destabilizing | 0.25 | N | 0.612 | neutral | None | None | None | None | N |
| R/F | 0.5848 | likely_pathogenic | 0.6076 | pathogenic | -1.16 | Destabilizing | 0.935 | D | 0.77 | deleterious | None | None | None | None | N |
| R/G | 0.4604 | ambiguous | 0.4939 | ambiguous | -2.046 | Highly Destabilizing | 0.334 | N | 0.693 | prob.neutral | N | 0.492911141 | None | None | N |
| R/H | 0.1207 | likely_benign | 0.1165 | benign | -1.952 | Destabilizing | 0.826 | D | 0.662 | neutral | None | None | None | None | N |
| R/I | 0.2787 | likely_benign | 0.2948 | benign | -0.706 | Destabilizing | 0.781 | D | 0.775 | deleterious | N | 0.455296902 | None | None | N |
| R/K | 0.114 | likely_benign | 0.1036 | benign | -1.406 | Destabilizing | 0.002 | N | 0.333 | neutral | N | 0.427955585 | None | None | N |
| R/L | 0.2969 | likely_benign | 0.3145 | benign | -0.706 | Destabilizing | 0.399 | N | 0.693 | prob.neutral | None | None | None | None | N |
| R/M | 0.3441 | ambiguous | 0.3642 | ambiguous | -1.086 | Destabilizing | 0.982 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/N | 0.6621 | likely_pathogenic | 0.6753 | pathogenic | -1.049 | Destabilizing | 0.7 | D | 0.649 | neutral | None | None | None | None | N |
| R/P | 0.9714 | likely_pathogenic | 0.9778 | pathogenic | -1.02 | Destabilizing | 0.826 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/Q | 0.1319 | likely_benign | 0.1316 | benign | -1.104 | Destabilizing | 0.539 | D | 0.658 | neutral | None | None | None | None | N |
| R/S | 0.5643 | likely_pathogenic | 0.5923 | pathogenic | -2.032 | Highly Destabilizing | 0.201 | N | 0.671 | neutral | N | 0.438479223 | None | None | N |
| R/T | 0.3127 | likely_benign | 0.3289 | benign | -1.638 | Destabilizing | 0.638 | D | 0.721 | prob.delet. | N | 0.434476126 | None | None | N |
| R/V | 0.3776 | ambiguous | 0.3893 | ambiguous | -1.02 | Destabilizing | 0.7 | D | 0.759 | deleterious | None | None | None | None | N |
| R/W | 0.2564 | likely_benign | 0.2815 | benign | -0.617 | Destabilizing | 0.982 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/Y | 0.4822 | ambiguous | 0.4921 | ambiguous | -0.43 | Destabilizing | 0.935 | D | 0.751 | 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.