Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13880 | 41863;41864;41865 | chr2:178635686;178635685;178635684 | chr2:179500413;179500412;179500411 |
| N2AB | 12239 | 36940;36941;36942 | chr2:178635686;178635685;178635684 | chr2:179500413;179500412;179500411 |
| N2A | 11312 | 34159;34160;34161 | chr2:178635686;178635685;178635684 | chr2:179500413;179500412;179500411 |
| N2B | 4815 | 14668;14669;14670 | chr2:178635686;178635685;178635684 | chr2:179500413;179500412;179500411 |
| Novex-1 | 4940 | 15043;15044;15045 | chr2:178635686;178635685;178635684 | chr2:179500413;179500412;179500411 |
| Novex-2 | 5007 | 15244;15245;15246 | chr2:178635686;178635685;178635684 | chr2:179500413;179500412;179500411 |
| 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 | rs1228888611  |
-0.766 | None | N | 0.158 | 0.075 | 0.187945064343 | gnomAD-2.1.1 | 4.34E-06 | None | None | None | None | N | None | 0 | 3.07E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs1228888611 |
-0.766 | None | N | 0.158 | 0.075 | 0.187945064343 | gnomAD-4.0.0 | 6.89641E-07 | None | None | None | None | N | None | 0 | 2.31278E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | None | None | 0.664 | N | 0.69 | 0.23 | 0.0611884634855 | gnomAD-4.0.0 | 2.06898E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71247E-06 | 0 | 0 |
| I/T | None | None | 0.361 | N | 0.654 | 0.269 | 0.468586609112 | gnomAD-4.0.0 | 1.62095E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.90612E-06 | 0 | 0 |
| I/V | None | None | 0.048 | N | 0.414 | 0.077 | 0.286081765059 | gnomAD-4.0.0 | 6.89641E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0412E-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 | 0.9194 | likely_pathogenic | 0.9122 | pathogenic | -2.284 | Highly Destabilizing | 0.236 | N | 0.609 | neutral | None | None | None | None | N |
| I/C | 0.9751 | likely_pathogenic | 0.9743 | pathogenic | -1.279 | Destabilizing | 0.984 | D | 0.688 | prob.delet. | None | None | None | None | N |
| I/D | 0.9986 | likely_pathogenic | 0.9986 | pathogenic | -2.324 | Highly Destabilizing | 0.942 | D | 0.823 | deleterious | None | None | None | None | N |
| I/E | 0.9954 | likely_pathogenic | 0.9952 | pathogenic | -2.142 | Highly Destabilizing | 0.842 | D | 0.808 | deleterious | None | None | None | None | N |
| I/F | 0.7229 | likely_pathogenic | 0.7417 | pathogenic | -1.321 | Destabilizing | 0.568 | D | 0.664 | prob.neutral | None | None | None | None | N |
| I/G | 0.9915 | likely_pathogenic | 0.9914 | pathogenic | -2.786 | Highly Destabilizing | 0.842 | D | 0.794 | deleterious | None | None | None | None | N |
| I/H | 0.9953 | likely_pathogenic | 0.9959 | pathogenic | -2.18 | Highly Destabilizing | 0.984 | D | 0.791 | deleterious | None | None | None | None | N |
| I/K | 0.9911 | likely_pathogenic | 0.9916 | pathogenic | -1.681 | Destabilizing | 0.8 | D | 0.783 | deleterious | N | 0.476253081 | None | None | N |
| I/L | 0.1201 | likely_benign | 0.1276 | benign | -0.859 | Destabilizing | None | N | 0.158 | neutral | N | 0.407013479 | None | None | N |
| I/M | 0.3142 | likely_benign | 0.3166 | benign | -0.635 | Destabilizing | 0.664 | D | 0.69 | prob.delet. | N | 0.476253081 | None | None | N |
| I/N | 0.9833 | likely_pathogenic | 0.9843 | pathogenic | -1.818 | Destabilizing | 0.942 | D | 0.825 | deleterious | None | None | None | None | N |
| I/P | 0.9391 | likely_pathogenic | 0.9103 | pathogenic | -1.312 | Destabilizing | 0.942 | D | 0.828 | deleterious | None | None | None | None | N |
| I/Q | 0.9908 | likely_pathogenic | 0.991 | pathogenic | -1.757 | Destabilizing | 0.942 | D | 0.815 | deleterious | None | None | None | None | N |
| I/R | 0.9876 | likely_pathogenic | 0.9882 | pathogenic | -1.352 | Destabilizing | 0.8 | D | 0.824 | deleterious | N | 0.476253081 | None | None | N |
| I/S | 0.9724 | likely_pathogenic | 0.9718 | pathogenic | -2.489 | Highly Destabilizing | 0.842 | D | 0.718 | prob.delet. | None | None | None | None | N |
| I/T | 0.9523 | likely_pathogenic | 0.9534 | pathogenic | -2.171 | Highly Destabilizing | 0.361 | N | 0.654 | prob.neutral | N | 0.475236508 | None | None | N |
| I/V | 0.1716 | likely_benign | 0.1643 | benign | -1.312 | Destabilizing | 0.048 | N | 0.414 | neutral | N | 0.472267162 | None | None | N |
| I/W | 0.9936 | likely_pathogenic | 0.9941 | pathogenic | -1.669 | Destabilizing | 0.984 | D | 0.797 | deleterious | None | None | None | None | N |
| I/Y | 0.9833 | likely_pathogenic | 0.9846 | pathogenic | -1.374 | Destabilizing | 0.842 | D | 0.748 | 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.