Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32329 | 97210;97211;97212 | chr2:178542869;178542868;178542867 | chr2:179407596;179407595;179407594 |
| N2AB | 30688 | 92287;92288;92289 | chr2:178542869;178542868;178542867 | chr2:179407596;179407595;179407594 |
| N2A | 29761 | 89506;89507;89508 | chr2:178542869;178542868;178542867 | chr2:179407596;179407595;179407594 |
| N2B | 23264 | 70015;70016;70017 | chr2:178542869;178542868;178542867 | chr2:179407596;179407595;179407594 |
| Novex-1 | 23389 | 70390;70391;70392 | chr2:178542869;178542868;178542867 | chr2:179407596;179407595;179407594 |
| Novex-2 | 23456 | 70591;70592;70593 | chr2:178542869;178542868;178542867 | chr2:179407596;179407595;179407594 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs759641873  |
-1.437 | 1.0 | N | 0.768 | 0.399 | None | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs759641873 |
-1.437 | 1.0 | N | 0.768 | 0.399 | None | gnomAD-4.0.0 | 1.36842E-06 | None | None | None | None | N | None | 2.98739E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| P/T | None | None | 1.0 | N | 0.762 | 0.402 | 0.429091045357 | gnomAD-4.0.0 | 6.84211E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65645E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2359 | likely_benign | 0.2144 | benign | -1.172 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.520858251 | None | None | N |
| P/C | 0.8617 | likely_pathogenic | 0.8083 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| P/D | 0.7277 | likely_pathogenic | 0.712 | pathogenic | -1.225 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| P/E | 0.6112 | likely_pathogenic | 0.5887 | pathogenic | -1.268 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| P/F | 0.8892 | likely_pathogenic | 0.853 | pathogenic | -0.993 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| P/G | 0.5494 | ambiguous | 0.5233 | ambiguous | -1.429 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| P/H | 0.5092 | ambiguous | 0.4387 | ambiguous | -1.005 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.528459014 | None | None | N |
| P/I | 0.8134 | likely_pathogenic | 0.7695 | pathogenic | -0.592 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| P/K | 0.6261 | likely_pathogenic | 0.5711 | pathogenic | -1.197 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| P/L | 0.4115 | ambiguous | 0.3573 | ambiguous | -0.592 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.482805947 | None | None | N |
| P/M | 0.7743 | likely_pathogenic | 0.7269 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| P/N | 0.6349 | likely_pathogenic | 0.5951 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| P/Q | 0.4306 | ambiguous | 0.3887 | ambiguous | -1.154 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| P/R | 0.4323 | ambiguous | 0.3709 | ambiguous | -0.597 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.48566824200000003 | None | None | N |
| P/S | 0.2999 | likely_benign | 0.2721 | benign | -1.328 | Destabilizing | 1.0 | D | 0.768 | deleterious | N | 0.508833103 | None | None | N |
| P/T | 0.3225 | likely_benign | 0.2936 | benign | -1.274 | Destabilizing | 1.0 | D | 0.762 | deleterious | N | 0.50709952 | None | None | N |
| P/V | 0.6321 | likely_pathogenic | 0.5851 | pathogenic | -0.75 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| P/W | 0.9315 | likely_pathogenic | 0.9047 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| P/Y | 0.8433 | likely_pathogenic | 0.7965 | pathogenic | -0.898 | Destabilizing | 1.0 | D | 0.763 | 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.