Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23232 | 69919;69920;69921 | chr2:178576550;178576549;178576548 | chr2:179441277;179441276;179441275 |
| N2AB | 21591 | 64996;64997;64998 | chr2:178576550;178576549;178576548 | chr2:179441277;179441276;179441275 |
| N2A | 20664 | 62215;62216;62217 | chr2:178576550;178576549;178576548 | chr2:179441277;179441276;179441275 |
| N2B | 14167 | 42724;42725;42726 | chr2:178576550;178576549;178576548 | chr2:179441277;179441276;179441275 |
| Novex-1 | 14292 | 43099;43100;43101 | chr2:178576550;178576549;178576548 | chr2:179441277;179441276;179441275 |
| Novex-2 | 14359 | 43300;43301;43302 | chr2:178576550;178576549;178576548 | chr2:179441277;179441276;179441275 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1575819357  |
None | 0.952 | N | 0.547 | 0.204 | 0.479363622381 | gnomAD-4.0.0 | 3.18409E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86854E-05 | 0 |
| V/L | rs1195674859 |
-0.188 | 0.802 | N | 0.557 | 0.186 | 0.321393169273 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/L | rs1195674859 |
-0.188 | 0.802 | N | 0.557 | 0.186 | 0.321393169273 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| V/L | rs1195674859 |
-0.188 | 0.802 | N | 0.557 | 0.186 | 0.321393169273 | gnomAD-4.0.0 | 5.57866E-06 | None | None | None | None | N | None | 1.33522E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.0864E-06 | 0 | 3.20307E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.262 | likely_benign | 0.2664 | benign | -1.688 | Destabilizing | 0.952 | D | 0.547 | neutral | N | 0.484808096 | None | None | N |
| V/C | 0.688 | likely_pathogenic | 0.703 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| V/D | 0.769 | likely_pathogenic | 0.8229 | pathogenic | -1.592 | Destabilizing | 0.998 | D | 0.872 | deleterious | N | 0.486075544 | None | None | N |
| V/E | 0.5896 | likely_pathogenic | 0.647 | pathogenic | -1.497 | Destabilizing | 0.998 | D | 0.889 | deleterious | None | None | None | None | N |
| V/F | 0.2032 | likely_benign | 0.2275 | benign | -1.105 | Destabilizing | 0.986 | D | 0.87 | deleterious | N | 0.46746431 | None | None | N |
| V/G | 0.423 | ambiguous | 0.469 | ambiguous | -2.113 | Highly Destabilizing | 0.998 | D | 0.873 | deleterious | N | 0.486075544 | None | None | N |
| V/H | 0.7293 | likely_pathogenic | 0.761 | pathogenic | -1.618 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| V/I | 0.0775 | likely_benign | 0.0773 | benign | -0.579 | Destabilizing | 0.058 | N | 0.283 | neutral | N | 0.469356703 | None | None | N |
| V/K | 0.5253 | ambiguous | 0.5646 | pathogenic | -1.46 | Destabilizing | 0.995 | D | 0.897 | deleterious | None | None | None | None | N |
| V/L | 0.2208 | likely_benign | 0.208 | benign | -0.579 | Destabilizing | 0.802 | D | 0.557 | neutral | N | 0.504565355 | None | None | N |
| V/M | 0.1675 | likely_benign | 0.1804 | benign | -0.468 | Destabilizing | 0.989 | D | 0.734 | deleterious | None | None | None | None | N |
| V/N | 0.6226 | likely_pathogenic | 0.6707 | pathogenic | -1.463 | Destabilizing | 0.998 | D | 0.874 | deleterious | None | None | None | None | N |
| V/P | 0.9177 | likely_pathogenic | 0.937 | pathogenic | -0.915 | Destabilizing | 0.998 | D | 0.889 | deleterious | None | None | None | None | N |
| V/Q | 0.5139 | ambiguous | 0.5504 | ambiguous | -1.486 | Destabilizing | 0.998 | D | 0.885 | deleterious | None | None | None | None | N |
| V/R | 0.4815 | ambiguous | 0.5212 | ambiguous | -1.046 | Destabilizing | 0.998 | D | 0.869 | deleterious | None | None | None | None | N |
| V/S | 0.4192 | ambiguous | 0.4524 | ambiguous | -2.078 | Highly Destabilizing | 0.995 | D | 0.891 | deleterious | None | None | None | None | N |
| V/T | 0.2632 | likely_benign | 0.276 | benign | -1.849 | Destabilizing | 0.963 | D | 0.653 | prob.neutral | None | None | None | None | N |
| V/W | 0.8907 | likely_pathogenic | 0.9071 | pathogenic | -1.413 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Y | 0.6579 | likely_pathogenic | 0.6874 | pathogenic | -1.073 | Destabilizing | 0.998 | D | 0.861 | 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.