Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15896 | 47911;47912;47913 | chr2:178617399;178617398;178617397 | chr2:179482126;179482125;179482124 |
| N2AB | 14255 | 42988;42989;42990 | chr2:178617399;178617398;178617397 | chr2:179482126;179482125;179482124 |
| N2A | 13328 | 40207;40208;40209 | chr2:178617399;178617398;178617397 | chr2:179482126;179482125;179482124 |
| N2B | 6831 | 20716;20717;20718 | chr2:178617399;178617398;178617397 | chr2:179482126;179482125;179482124 |
| Novex-1 | 6956 | 21091;21092;21093 | chr2:178617399;178617398;178617397 | chr2:179482126;179482125;179482124 |
| Novex-2 | 7023 | 21292;21293;21294 | chr2:178617399;178617398;178617397 | chr2:179482126;179482125;179482124 |
| 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/L | None | None | 0.294 | N | 0.383 | 0.111 | 0.608094534769 | gnomAD-4.0.0 | 6.94501E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.89258E-05 | 0 | 0 | 0 | 0 |
| I/T | rs1411457226  |
-3.457 | 0.822 | D | 0.705 | 0.459 | 0.838609721794 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1411457226 |
-3.457 | 0.822 | D | 0.705 | 0.459 | 0.838609721794 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1411457226 |
-3.457 | 0.822 | D | 0.705 | 0.459 | 0.838609721794 | gnomAD-4.0.0 | 3.14099E-06 | None | None | None | None | N | None | 1.35523E-05 | 0 | None | 0 | 4.51875E-05 | None | 0 | 0 | 1.7068E-06 | 0 | 0 |
| I/V | None | None | 0.006 | N | 0.237 | 0.035 | 0.321108458156 | gnomAD-4.0.0 | 6.94501E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.05897E-07 | 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 | 0.7387 | likely_pathogenic | 0.8828 | pathogenic | -3.143 | Highly Destabilizing | 0.754 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.9413 | likely_pathogenic | 0.9717 | pathogenic | -2.284 | Highly Destabilizing | 0.994 | D | 0.772 | deleterious | None | None | None | None | N |
| I/D | 0.9978 | likely_pathogenic | 0.9989 | pathogenic | -3.776 | Highly Destabilizing | 0.993 | D | 0.899 | deleterious | None | None | None | None | N |
| I/E | 0.9912 | likely_pathogenic | 0.9953 | pathogenic | -3.46 | Highly Destabilizing | 0.978 | D | 0.893 | deleterious | None | None | None | None | N |
| I/F | 0.7041 | likely_pathogenic | 0.814 | pathogenic | -1.826 | Destabilizing | 0.942 | D | 0.678 | prob.neutral | D | 0.749053784 | None | None | N |
| I/G | 0.9799 | likely_pathogenic | 0.9923 | pathogenic | -3.729 | Highly Destabilizing | 0.978 | D | 0.891 | deleterious | None | None | None | None | N |
| I/H | 0.992 | likely_pathogenic | 0.9959 | pathogenic | -3.296 | Highly Destabilizing | 0.998 | D | 0.884 | deleterious | None | None | None | None | N |
| I/K | 0.9823 | likely_pathogenic | 0.9898 | pathogenic | -2.441 | Highly Destabilizing | 0.978 | D | 0.897 | deleterious | None | None | None | None | N |
| I/L | 0.2699 | likely_benign | 0.3659 | ambiguous | -1.363 | Destabilizing | 0.294 | N | 0.383 | neutral | N | 0.489660361 | None | None | N |
| I/M | 0.3509 | ambiguous | 0.4772 | ambiguous | -1.553 | Destabilizing | 0.942 | D | 0.657 | neutral | D | 0.629499091 | None | None | N |
| I/N | 0.9743 | likely_pathogenic | 0.9859 | pathogenic | -3.131 | Highly Destabilizing | 0.99 | D | 0.904 | deleterious | D | 0.750292538 | None | None | N |
| I/P | 0.9818 | likely_pathogenic | 0.9867 | pathogenic | -1.951 | Destabilizing | 0.993 | D | 0.902 | deleterious | None | None | None | None | N |
| I/Q | 0.9853 | likely_pathogenic | 0.992 | pathogenic | -2.798 | Highly Destabilizing | 0.993 | D | 0.905 | deleterious | None | None | None | None | N |
| I/R | 0.9713 | likely_pathogenic | 0.982 | pathogenic | -2.38 | Highly Destabilizing | 0.978 | D | 0.904 | deleterious | None | None | None | None | N |
| I/S | 0.9245 | likely_pathogenic | 0.9639 | pathogenic | -3.666 | Highly Destabilizing | 0.942 | D | 0.839 | deleterious | D | 0.750292538 | None | None | N |
| I/T | 0.5985 | likely_pathogenic | 0.8054 | pathogenic | -3.2 | Highly Destabilizing | 0.822 | D | 0.705 | prob.neutral | D | 0.749053784 | None | None | N |
| I/V | 0.0869 | likely_benign | 0.1081 | benign | -1.951 | Destabilizing | 0.006 | N | 0.237 | neutral | N | 0.459147576 | None | None | N |
| I/W | 0.9906 | likely_pathogenic | 0.9956 | pathogenic | -2.22 | Highly Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Y | 0.9748 | likely_pathogenic | 0.9869 | pathogenic | -2.1 | Highly Destabilizing | 0.978 | D | 0.767 | 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.