Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23072 | 69439;69440;69441 | chr2:178577121;178577120;178577119 | chr2:179441848;179441847;179441846 |
| N2AB | 21431 | 64516;64517;64518 | chr2:178577121;178577120;178577119 | chr2:179441848;179441847;179441846 |
| N2A | 20504 | 61735;61736;61737 | chr2:178577121;178577120;178577119 | chr2:179441848;179441847;179441846 |
| N2B | 14007 | 42244;42245;42246 | chr2:178577121;178577120;178577119 | chr2:179441848;179441847;179441846 |
| Novex-1 | 14132 | 42619;42620;42621 | chr2:178577121;178577120;178577119 | chr2:179441848;179441847;179441846 |
| Novex-2 | 14199 | 42820;42821;42822 | chr2:178577121;178577120;178577119 | chr2:179441848;179441847;179441846 |
| 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 | rs374117511  |
-0.843 | 0.991 | D | 0.727 | 0.41 | None | gnomAD-2.1.1 | 5.24E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.15842E-04 | 0 |
| I/M | rs374117511 |
-0.843 | 0.991 | D | 0.727 | 0.41 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/M | rs374117511 |
-0.843 | 0.991 | D | 0.727 | 0.41 | None | gnomAD-4.0.0 | 3.46172E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.50711E-05 | 1.34077E-05 | 8.53777E-05 |
| I/N | rs1309205725 |
-1.646 | 0.997 | D | 0.819 | 0.578 | 0.897848762137 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs1309205725 |
-1.646 | 0.997 | D | 0.819 | 0.578 | 0.897848762137 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs1309205725 |
-1.646 | 0.997 | D | 0.819 | 0.578 | 0.897848762137 | gnomAD-4.0.0 | 7.43903E-06 | None | None | None | None | I | None | 1.33608E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32575E-06 | 0 | 0 |
| I/V | rs2046609808 |
None | 0.02 | N | 0.244 | 0.112 | 0.433491693731 | gnomAD-4.0.0 | 3.18451E-06 | None | None | None | None | I | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 0 | 0 | 2.86E-06 | 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 | 0.9347 | likely_pathogenic | 0.9481 | pathogenic | -2.279 | Highly Destabilizing | 0.91 | D | 0.677 | prob.neutral | None | None | None | None | I |
| I/C | 0.9507 | likely_pathogenic | 0.9584 | pathogenic | -1.445 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | I |
| I/D | 0.9978 | likely_pathogenic | 0.9985 | pathogenic | -2.051 | Highly Destabilizing | 0.998 | D | 0.81 | deleterious | None | None | None | None | I |
| I/E | 0.9907 | likely_pathogenic | 0.9925 | pathogenic | -1.95 | Destabilizing | 0.993 | D | 0.81 | deleterious | None | None | None | None | I |
| I/F | 0.8841 | likely_pathogenic | 0.9112 | pathogenic | -1.512 | Destabilizing | 0.991 | D | 0.755 | deleterious | D | 0.560416164 | None | None | I |
| I/G | 0.9893 | likely_pathogenic | 0.9929 | pathogenic | -2.715 | Highly Destabilizing | 0.993 | D | 0.8 | deleterious | None | None | None | None | I |
| I/H | 0.9938 | likely_pathogenic | 0.9954 | pathogenic | -1.986 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | I |
| I/K | 0.9851 | likely_pathogenic | 0.987 | pathogenic | -1.654 | Destabilizing | 0.993 | D | 0.808 | deleterious | None | None | None | None | I |
| I/L | 0.2626 | likely_benign | 0.2707 | benign | -1.085 | Destabilizing | 0.58 | D | 0.461 | neutral | N | 0.485023403 | None | None | I |
| I/M | 0.466 | ambiguous | 0.5173 | ambiguous | -0.824 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | D | 0.551594754 | None | None | I |
| I/N | 0.969 | likely_pathogenic | 0.9761 | pathogenic | -1.651 | Destabilizing | 0.997 | D | 0.819 | deleterious | D | 0.563965018 | None | None | I |
| I/P | 0.9488 | likely_pathogenic | 0.9499 | pathogenic | -1.457 | Destabilizing | 0.998 | D | 0.821 | deleterious | None | None | None | None | I |
| I/Q | 0.9852 | likely_pathogenic | 0.988 | pathogenic | -1.72 | Destabilizing | 0.998 | D | 0.815 | deleterious | None | None | None | None | I |
| I/R | 0.9802 | likely_pathogenic | 0.9835 | pathogenic | -1.12 | Destabilizing | 0.998 | D | 0.815 | deleterious | None | None | None | None | I |
| I/S | 0.967 | likely_pathogenic | 0.9765 | pathogenic | -2.346 | Highly Destabilizing | 0.991 | D | 0.774 | deleterious | D | 0.551848244 | None | None | I |
| I/T | 0.9291 | likely_pathogenic | 0.9316 | pathogenic | -2.118 | Highly Destabilizing | 0.939 | D | 0.765 | deleterious | D | 0.531110643 | None | None | I |
| I/V | 0.0698 | likely_benign | 0.0756 | benign | -1.457 | Destabilizing | 0.02 | N | 0.244 | neutral | N | 0.491279132 | None | None | I |
| I/W | 0.997 | likely_pathogenic | 0.9979 | pathogenic | -1.732 | Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | I |
| I/Y | 0.9861 | likely_pathogenic | 0.9897 | pathogenic | -1.492 | Destabilizing | 0.998 | D | 0.764 | deleterious | None | None | None | None | I |
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.