Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19833 | 59722;59723;59724 | chr2:178592508;178592507;178592506 | chr2:179457235;179457234;179457233 |
| N2AB | 18192 | 54799;54800;54801 | chr2:178592508;178592507;178592506 | chr2:179457235;179457234;179457233 |
| N2A | 17265 | 52018;52019;52020 | chr2:178592508;178592507;178592506 | chr2:179457235;179457234;179457233 |
| N2B | 10768 | 32527;32528;32529 | chr2:178592508;178592507;178592506 | chr2:179457235;179457234;179457233 |
| Novex-1 | 10893 | 32902;32903;32904 | chr2:178592508;178592507;178592506 | chr2:179457235;179457234;179457233 |
| Novex-2 | 10960 | 33103;33104;33105 | chr2:178592508;178592507;178592506 | chr2:179457235;179457234;179457233 |
| 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 | rs2050442222  |
None | 0.104 | D | 0.237 | 0.214 | 0.32082282376 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs2050442222 |
None | 0.104 | D | 0.237 | 0.214 | 0.32082282376 | gnomAD-4.0.0 | 2.56307E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.85625E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | None | None | 0.999 | N | 0.724 | 0.554 | 0.904533080692 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.17284E-04 | 0 | 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 | 0.5621 | ambiguous | 0.4873 | ambiguous | -1.689 | Destabilizing | 0.996 | D | 0.559 | neutral | None | None | None | None | N |
| I/C | 0.8355 | likely_pathogenic | 0.7867 | pathogenic | -0.979 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/D | 0.956 | likely_pathogenic | 0.9348 | pathogenic | -1.242 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| I/E | 0.8118 | likely_pathogenic | 0.7549 | pathogenic | -1.204 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/F | 0.3515 | ambiguous | 0.2869 | benign | -1.118 | Destabilizing | 0.997 | D | 0.633 | neutral | N | 0.483224021 | None | None | N |
| I/G | 0.892 | likely_pathogenic | 0.8585 | pathogenic | -2.04 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| I/H | 0.844 | likely_pathogenic | 0.7891 | pathogenic | -1.167 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| I/K | 0.6631 | likely_pathogenic | 0.5659 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| I/L | 0.2581 | likely_benign | 0.2108 | benign | -0.784 | Destabilizing | 0.104 | N | 0.237 | neutral | D | 0.527016219 | None | None | N |
| I/M | 0.1316 | likely_benign | 0.1141 | benign | -0.632 | Destabilizing | 0.997 | D | 0.665 | neutral | D | 0.528923161 | None | None | N |
| I/N | 0.7262 | likely_pathogenic | 0.6376 | pathogenic | -1.097 | Destabilizing | 0.999 | D | 0.818 | deleterious | N | 0.517550108 | None | None | N |
| I/P | 0.9157 | likely_pathogenic | 0.9156 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/Q | 0.6994 | likely_pathogenic | 0.6268 | pathogenic | -1.22 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| I/R | 0.5922 | likely_pathogenic | 0.5006 | ambiguous | -0.618 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/S | 0.6403 | likely_pathogenic | 0.5647 | pathogenic | -1.693 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | N | 0.501812483 | None | None | N |
| I/T | 0.3261 | likely_benign | 0.2425 | benign | -1.529 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | N | 0.494557554 | None | None | N |
| I/V | 0.1138 | likely_benign | 0.0923 | benign | -1.056 | Destabilizing | 0.889 | D | 0.371 | neutral | N | 0.470296145 | None | None | N |
| I/W | 0.8533 | likely_pathogenic | 0.8369 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| I/Y | 0.7703 | likely_pathogenic | 0.7239 | pathogenic | -0.992 | Destabilizing | 1.0 | D | 0.742 | 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.