Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19291 | 58096;58097;58098 | chr2:178594623;178594622;178594621 | chr2:179459350;179459349;179459348 |
| N2AB | 17650 | 53173;53174;53175 | chr2:178594623;178594622;178594621 | chr2:179459350;179459349;179459348 |
| N2A | 16723 | 50392;50393;50394 | chr2:178594623;178594622;178594621 | chr2:179459350;179459349;179459348 |
| N2B | 10226 | 30901;30902;30903 | chr2:178594623;178594622;178594621 | chr2:179459350;179459349;179459348 |
| Novex-1 | 10351 | 31276;31277;31278 | chr2:178594623;178594622;178594621 | chr2:179459350;179459349;179459348 |
| Novex-2 | 10418 | 31477;31478;31479 | chr2:178594623;178594622;178594621 | chr2:179459350;179459349;179459348 |
| 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/M | None | None | 0.999 | N | 0.793 | 0.369 | 0.528662862717 | gnomAD-4.0.0 | 6.85515E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00778E-07 | 0 | 0 |
| L/Q | None | None | 1.0 | D | 0.893 | 0.58 | 0.862648291891 | gnomAD-4.0.0 | 1.59786E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87054E-06 | 0 | 0 |
| L/V | rs773843429  |
-1.596 | 0.619 | N | 0.449 | 0.218 | 0.254761474806 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.62E-05 | None | 0 | 0 | 0 |
| L/V | rs773843429 |
-1.596 | 0.619 | N | 0.449 | 0.218 | 0.254761474806 | gnomAD-4.0.0 | 1.37103E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.33051E-05 | 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 | 0.941 | likely_pathogenic | 0.9415 | pathogenic | -2.569 | Highly Destabilizing | 0.994 | D | 0.747 | deleterious | None | None | None | None | N |
| L/C | 0.8991 | likely_pathogenic | 0.9097 | pathogenic | -2.396 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -3.061 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| L/E | 0.9967 | likely_pathogenic | 0.9963 | pathogenic | -2.899 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/F | 0.7836 | likely_pathogenic | 0.7513 | pathogenic | -1.66 | Destabilizing | 0.999 | D | 0.828 | deleterious | None | None | None | None | N |
| L/G | 0.9926 | likely_pathogenic | 0.992 | pathogenic | -3.052 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| L/H | 0.9937 | likely_pathogenic | 0.9924 | pathogenic | -2.398 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| L/I | 0.1943 | likely_benign | 0.194 | benign | -1.198 | Destabilizing | 0.988 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/K | 0.9934 | likely_pathogenic | 0.9927 | pathogenic | -1.983 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| L/M | 0.3869 | ambiguous | 0.4072 | ambiguous | -1.404 | Destabilizing | 0.999 | D | 0.793 | deleterious | N | 0.509744839 | None | None | N |
| L/N | 0.9946 | likely_pathogenic | 0.9948 | pathogenic | -2.248 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| L/P | 0.9828 | likely_pathogenic | 0.9761 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.899 | deleterious | N | 0.485705527 | None | None | N |
| L/Q | 0.9895 | likely_pathogenic | 0.988 | pathogenic | -2.239 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.525735954 | None | None | N |
| L/R | 0.9889 | likely_pathogenic | 0.9863 | pathogenic | -1.584 | Destabilizing | 1.0 | D | 0.887 | deleterious | N | 0.519152588 | None | None | N |
| L/S | 0.9926 | likely_pathogenic | 0.9926 | pathogenic | -2.921 | Highly Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| L/T | 0.905 | likely_pathogenic | 0.9079 | pathogenic | -2.62 | Highly Destabilizing | 0.998 | D | 0.787 | deleterious | None | None | None | None | N |
| L/V | 0.1556 | likely_benign | 0.1546 | benign | -1.634 | Destabilizing | 0.619 | D | 0.449 | neutral | N | 0.462324449 | None | None | N |
| L/W | 0.9832 | likely_pathogenic | 0.9771 | pathogenic | -1.94 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| L/Y | 0.9875 | likely_pathogenic | 0.9851 | pathogenic | -1.692 | Destabilizing | 1.0 | D | 0.839 | 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.