Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29017 | 87274;87275;87276 | chr2:178558410;178558409;178558408 | chr2:179423137;179423136;179423135 |
| N2AB | 27376 | 82351;82352;82353 | chr2:178558410;178558409;178558408 | chr2:179423137;179423136;179423135 |
| N2A | 26449 | 79570;79571;79572 | chr2:178558410;178558409;178558408 | chr2:179423137;179423136;179423135 |
| N2B | 19952 | 60079;60080;60081 | chr2:178558410;178558409;178558408 | chr2:179423137;179423136;179423135 |
| Novex-1 | 20077 | 60454;60455;60456 | chr2:178558410;178558409;178558408 | chr2:179423137;179423136;179423135 |
| Novex-2 | 20144 | 60655;60656;60657 | chr2:178558410;178558409;178558408 | chr2:179423137;179423136;179423135 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs727505050  |
None | 1.0 | D | 0.804 | 0.723 | 0.641425284928 | gnomAD-4.0.0 | 2.05277E-06 | None | None | None | None | N | None | 0 | 2.23604E-05 | None | 0 | 0 | None | 0 | 0 | 1.79891E-06 | 0 | 0 |
| A/V | rs1454476732 |
-0.907 | 1.0 | D | 0.703 | 0.664 | 0.795736422416 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/V | rs1454476732 |
-0.907 | 1.0 | D | 0.703 | 0.664 | 0.795736422416 | gnomAD-4.0.0 | 1.59147E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43299E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8474 | likely_pathogenic | 0.7993 | pathogenic | -1.763 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| A/D | 0.9989 | likely_pathogenic | 0.9988 | pathogenic | -2.628 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | D | 0.648256847 | None | None | N |
| A/E | 0.9975 | likely_pathogenic | 0.9976 | pathogenic | -2.393 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/F | 0.9947 | likely_pathogenic | 0.995 | pathogenic | -0.75 | Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| A/G | 0.5282 | ambiguous | 0.5219 | ambiguous | -2.469 | Highly Destabilizing | 1.0 | D | 0.603 | neutral | D | 0.601602471 | None | None | N |
| A/H | 0.9979 | likely_pathogenic | 0.9979 | pathogenic | -2.16 | Highly Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| A/I | 0.9818 | likely_pathogenic | 0.981 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| A/K | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.488 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/L | 0.9365 | likely_pathogenic | 0.9413 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| A/M | 0.9711 | likely_pathogenic | 0.9702 | pathogenic | -1.368 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| A/N | 0.9965 | likely_pathogenic | 0.9956 | pathogenic | -1.921 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| A/P | 0.9721 | likely_pathogenic | 0.9844 | pathogenic | -1.249 | Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.622113323 | None | None | N |
| A/Q | 0.9921 | likely_pathogenic | 0.9927 | pathogenic | -1.607 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| A/R | 0.9957 | likely_pathogenic | 0.9963 | pathogenic | -1.583 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| A/S | 0.3226 | likely_benign | 0.2606 | benign | -2.298 | Highly Destabilizing | 1.0 | D | 0.597 | neutral | D | 0.565708031 | None | None | N |
| A/T | 0.7367 | likely_pathogenic | 0.6655 | pathogenic | -1.962 | Destabilizing | 1.0 | D | 0.804 | deleterious | D | 0.615209104 | None | None | N |
| A/V | 0.8767 | likely_pathogenic | 0.8629 | pathogenic | -1.249 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.630623052 | None | None | N |
| A/W | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| A/Y | 0.998 | likely_pathogenic | 0.9981 | pathogenic | -1.097 | Destabilizing | 1.0 | D | 0.919 | 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.