Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14605 | 44038;44039;44040 | chr2:178631235;178631234;178631233 | chr2:179495962;179495961;179495960 |
| N2AB | 12964 | 39115;39116;39117 | chr2:178631235;178631234;178631233 | chr2:179495962;179495961;179495960 |
| N2A | 12037 | 36334;36335;36336 | chr2:178631235;178631234;178631233 | chr2:179495962;179495961;179495960 |
| N2B | 5540 | 16843;16844;16845 | chr2:178631235;178631234;178631233 | chr2:179495962;179495961;179495960 |
| Novex-1 | 5665 | 17218;17219;17220 | chr2:178631235;178631234;178631233 | chr2:179495962;179495961;179495960 |
| Novex-2 | 5732 | 17419;17420;17421 | chr2:178631235;178631234;178631233 | chr2:179495962;179495961;179495960 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs1251970273  |
-0.248 | 0.996 | D | 0.616 | 0.608 | 0.558147714631 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| L/I | rs1251970273 |
-0.248 | 0.996 | D | 0.616 | 0.608 | 0.558147714631 | gnomAD-4.0.0 | 2.05409E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69921E-06 | 0 | 0 |
| L/P | None | None | 1.0 | D | 0.877 | 0.886 | 0.924476627806 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.958 | likely_pathogenic | 0.9645 | pathogenic | -2.369 | Highly Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| L/C | 0.9362 | likely_pathogenic | 0.948 | pathogenic | -1.475 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -3.164 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/E | 0.9939 | likely_pathogenic | 0.9951 | pathogenic | -2.863 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/F | 0.2166 | likely_benign | 0.2109 | benign | -1.52 | Destabilizing | 0.702 | D | 0.449 | neutral | None | None | None | None | N |
| L/G | 0.9909 | likely_pathogenic | 0.992 | pathogenic | -2.907 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/H | 0.9647 | likely_pathogenic | 0.9684 | pathogenic | -2.707 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/I | 0.2136 | likely_benign | 0.2355 | benign | -0.74 | Destabilizing | 0.996 | D | 0.616 | neutral | D | 0.628364433 | None | None | N |
| L/K | 0.9852 | likely_pathogenic | 0.9882 | pathogenic | -1.89 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/M | 0.3141 | likely_benign | 0.3098 | benign | -0.873 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| L/N | 0.9955 | likely_pathogenic | 0.9959 | pathogenic | -2.632 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/P | 0.9937 | likely_pathogenic | 0.9945 | pathogenic | -1.277 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.826815369 | None | None | N |
| L/Q | 0.9651 | likely_pathogenic | 0.9711 | pathogenic | -2.254 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.826815369 | None | None | N |
| L/R | 0.9639 | likely_pathogenic | 0.9726 | pathogenic | -2.102 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | D | 0.826815369 | None | None | N |
| L/S | 0.9873 | likely_pathogenic | 0.9889 | pathogenic | -3.046 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/T | 0.9711 | likely_pathogenic | 0.9741 | pathogenic | -2.59 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/V | 0.3786 | ambiguous | 0.4039 | ambiguous | -1.277 | Destabilizing | 0.996 | D | 0.639 | neutral | D | 0.698669728 | None | None | N |
| L/W | 0.8078 | likely_pathogenic | 0.8276 | pathogenic | -1.852 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/Y | 0.8834 | likely_pathogenic | 0.8896 | pathogenic | -1.655 | Destabilizing | 0.998 | D | 0.835 | 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.