Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33627 | 101104;101105;101106 | chr2:178535736;178535735;178535734 | chr2:179400463;179400462;179400461 |
| N2AB | 31986 | 96181;96182;96183 | chr2:178535736;178535735;178535734 | chr2:179400463;179400462;179400461 |
| N2A | 31059 | 93400;93401;93402 | chr2:178535736;178535735;178535734 | chr2:179400463;179400462;179400461 |
| N2B | 24562 | 73909;73910;73911 | chr2:178535736;178535735;178535734 | chr2:179400463;179400462;179400461 |
| Novex-1 | 24687 | 74284;74285;74286 | chr2:178535736;178535735;178535734 | chr2:179400463;179400462;179400461 |
| Novex-2 | 24754 | 74485;74486;74487 | chr2:178535736;178535735;178535734 | chr2:179400463;179400462;179400461 |
| 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/M | rs756942845  |
-0.8 | 0.999 | N | 0.696 | 0.655 | 0.612784651154 | gnomAD-2.1.1 | 7.14E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56306E-04 | 0 |
| I/M | rs756942845 |
-0.8 | 0.999 | N | 0.696 | 0.655 | 0.612784651154 | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.05822E-04 | 0 | 0 |
| I/M | rs756942845 |
-0.8 | 0.999 | N | 0.696 | 0.655 | 0.612784651154 | gnomAD-4.0.0 | 1.05359E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44099E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9904 | likely_pathogenic | 0.9803 | pathogenic | -2.024 | Highly Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/C | 0.9935 | likely_pathogenic | 0.9876 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/D | 0.9998 | likely_pathogenic | 0.9996 | pathogenic | -1.876 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| I/E | 0.9992 | likely_pathogenic | 0.9984 | pathogenic | -1.756 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| I/F | 0.9411 | likely_pathogenic | 0.8755 | pathogenic | -1.258 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.50560528 | None | None | N |
| I/G | 0.9991 | likely_pathogenic | 0.9982 | pathogenic | -2.468 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| I/H | 0.9994 | likely_pathogenic | 0.9987 | pathogenic | -1.821 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| I/K | 0.9984 | likely_pathogenic | 0.9966 | pathogenic | -1.525 | Destabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| I/L | 0.7167 | likely_pathogenic | 0.5008 | ambiguous | -0.807 | Destabilizing | 0.764 | D | 0.449 | neutral | N | 0.491082196 | None | None | N |
| I/M | 0.7635 | likely_pathogenic | 0.586 | pathogenic | -0.603 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | N | 0.521760979 | None | None | N |
| I/N | 0.9968 | likely_pathogenic | 0.9939 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.533624263 | None | None | N |
| I/P | 0.9966 | likely_pathogenic | 0.9951 | pathogenic | -1.186 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| I/Q | 0.9988 | likely_pathogenic | 0.9971 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| I/R | 0.9979 | likely_pathogenic | 0.9953 | pathogenic | -1.097 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| I/S | 0.9956 | likely_pathogenic | 0.9916 | pathogenic | -2.182 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | N | 0.515266519 | None | None | N |
| I/T | 0.9856 | likely_pathogenic | 0.9711 | pathogenic | -1.93 | Destabilizing | 0.997 | D | 0.773 | deleterious | N | 0.510240089 | None | None | N |
| I/V | 0.2348 | likely_benign | 0.1751 | benign | -1.186 | Destabilizing | 0.211 | N | 0.209 | neutral | N | 0.463881887 | None | None | N |
| I/W | 0.9993 | likely_pathogenic | 0.9986 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| I/Y | 0.9971 | likely_pathogenic | 0.9938 | pathogenic | -1.241 | Destabilizing | 0.999 | D | 0.745 | 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.