Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24343 | 73252;73253;73254 | chr2:178573105;178573104;178573103 | chr2:179437832;179437831;179437830 |
| N2AB | 22702 | 68329;68330;68331 | chr2:178573105;178573104;178573103 | chr2:179437832;179437831;179437830 |
| N2A | 21775 | 65548;65549;65550 | chr2:178573105;178573104;178573103 | chr2:179437832;179437831;179437830 |
| N2B | 15278 | 46057;46058;46059 | chr2:178573105;178573104;178573103 | chr2:179437832;179437831;179437830 |
| Novex-1 | 15403 | 46432;46433;46434 | chr2:178573105;178573104;178573103 | chr2:179437832;179437831;179437830 |
| Novex-2 | 15470 | 46633;46634;46635 | chr2:178573105;178573104;178573103 | chr2:179437832;179437831;179437830 |
| 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/G | None | None | 0.014 | N | 0.4 | 0.24 | 0.351180957027 | 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 |
| A/S | rs72646895  |
-1.392 | 0.514 | N | 0.448 | 0.141 | 0.231873229951 | 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/S | rs72646895 |
-1.392 | 0.514 | N | 0.448 | 0.141 | 0.231873229951 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52729E-05 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| A/T | rs72646895 |
-1.112 | 0.929 | N | 0.585 | 0.139 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 4.14E-05 | 1.41555E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.56E-05 | 1.40805E-04 |
| A/T | rs72646895 |
-1.112 | 0.929 | N | 0.585 | 0.139 | None | gnomAD-3.1.2 | 1.71077E-04 | None | None | None | None | N | None | 1.20761E-04 | 1.18126E-03 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07641E-04 | 0 |
| A/T | rs72646895 |
-1.112 | 0.929 | N | 0.585 | 0.139 | None | gnomAD-4.0.0 | 3.71961E-05 | None | None | None | None | N | None | 1.2025E-04 | 3.83704E-04 | None | 0 | 6.70901E-05 | None | 0 | 0 | 1.44126E-05 | 6.58892E-05 | 3.20369E-05 |
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 | 0.4238 | ambiguous | 0.4304 | ambiguous | -1.063 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| A/D | 0.7787 | likely_pathogenic | 0.7797 | pathogenic | -1.819 | Destabilizing | 0.942 | D | 0.712 | prob.delet. | N | 0.468317365 | None | None | N |
| A/E | 0.6119 | likely_pathogenic | 0.6183 | pathogenic | -1.693 | Destabilizing | 0.956 | D | 0.7 | prob.neutral | None | None | None | None | N |
| A/F | 0.497 | ambiguous | 0.5094 | ambiguous | -0.774 | Destabilizing | 0.956 | D | 0.775 | deleterious | None | None | None | None | N |
| A/G | 0.172 | likely_benign | 0.1634 | benign | -1.427 | Destabilizing | 0.014 | N | 0.4 | neutral | N | 0.499663755 | None | None | N |
| A/H | 0.6789 | likely_pathogenic | 0.7018 | pathogenic | -1.755 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| A/I | 0.3563 | ambiguous | 0.3655 | ambiguous | 0.068 | Stabilizing | 0.915 | D | 0.707 | prob.neutral | None | None | None | None | N |
| A/K | 0.7486 | likely_pathogenic | 0.7851 | pathogenic | -1.122 | Destabilizing | 0.956 | D | 0.699 | prob.neutral | None | None | None | None | N |
| A/L | 0.2696 | likely_benign | 0.2993 | benign | 0.068 | Stabilizing | 0.754 | D | 0.628 | neutral | None | None | None | None | N |
| A/M | 0.2846 | likely_benign | 0.3082 | benign | -0.097 | Destabilizing | 0.994 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/N | 0.4448 | ambiguous | 0.4942 | ambiguous | -1.211 | Destabilizing | 0.956 | D | 0.753 | deleterious | None | None | None | None | N |
| A/P | 0.9648 | likely_pathogenic | 0.9788 | pathogenic | -0.246 | Destabilizing | 0.988 | D | 0.727 | prob.delet. | N | 0.495829369 | None | None | N |
| A/Q | 0.5013 | ambiguous | 0.5144 | ambiguous | -1.137 | Destabilizing | 0.978 | D | 0.721 | prob.delet. | None | None | None | None | N |
| A/R | 0.6508 | likely_pathogenic | 0.6974 | pathogenic | -1.086 | Destabilizing | 0.978 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/S | 0.1049 | likely_benign | 0.0966 | benign | -1.66 | Destabilizing | 0.514 | D | 0.448 | neutral | N | 0.392029283 | None | None | N |
| A/T | 0.1165 | likely_benign | 0.1195 | benign | -1.415 | Destabilizing | 0.929 | D | 0.585 | neutral | N | 0.451253732 | None | None | N |
| A/V | 0.2207 | likely_benign | 0.2231 | benign | -0.246 | Destabilizing | 0.032 | N | 0.435 | neutral | N | 0.515537284 | None | None | N |
| A/W | 0.8842 | likely_pathogenic | 0.8986 | pathogenic | -1.417 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| A/Y | 0.6557 | likely_pathogenic | 0.6751 | pathogenic | -0.882 | Destabilizing | 0.978 | D | 0.765 | 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.