Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33487 | 100684;100685;100686 | chr2:178536288;178536287;178536286 | chr2:179401015;179401014;179401013 |
| N2AB | 31846 | 95761;95762;95763 | chr2:178536288;178536287;178536286 | chr2:179401015;179401014;179401013 |
| N2A | 30919 | 92980;92981;92982 | chr2:178536288;178536287;178536286 | chr2:179401015;179401014;179401013 |
| N2B | 24422 | 73489;73490;73491 | chr2:178536288;178536287;178536286 | chr2:179401015;179401014;179401013 |
| Novex-1 | 24547 | 73864;73865;73866 | chr2:178536288;178536287;178536286 | chr2:179401015;179401014;179401013 |
| Novex-2 | 24614 | 74065;74066;74067 | chr2:178536288;178536287;178536286 | chr2:179401015;179401014;179401013 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs72629779  |
-2.968 | 1.0 | N | 0.78 | 0.352 | None | gnomAD-2.1.1 | 3.74817E-03 | None | None | None | None | N | None | 3.93463E-02 | 2.1553E-03 | None | 0 | 0 | None | 0 | None | 0 | 7.81E-05 | 1.68871E-03 |
| P/S | rs72629779 |
-2.968 | 1.0 | N | 0.78 | 0.352 | None | gnomAD-3.1.2 | 1.12065E-02 | None | None | None | None | N | None | 3.86064E-02 | 4.91095E-03 | 0 | 0 | 0 | None | 0 | 0 | 1.17595E-04 | 0 | 1.09943E-02 |
| P/S | rs72629779 |
-2.968 | 1.0 | N | 0.78 | 0.352 | None | 1000 genomes | 1.3778E-02 | None | None | None | None | N | None | 4.99E-02 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/S | rs72629779 |
-2.968 | 1.0 | N | 0.78 | 0.352 | None | gnomAD-4.0.0 | 2.0934E-03 | None | None | None | None | N | None | 3.92902E-02 | 3.08436E-03 | None | 0 | 0 | None | 0 | 1.81458E-03 | 3.30577E-05 | 4.39232E-05 | 3.07338E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2926 | likely_benign | 0.3232 | benign | -2.32 | Highly Destabilizing | 0.999 | D | 0.824 | deleterious | N | 0.476628115 | None | None | N |
| P/C | 0.8263 | likely_pathogenic | 0.8331 | pathogenic | -2.326 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| P/D | 0.9933 | likely_pathogenic | 0.9967 | pathogenic | -3.36 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| P/E | 0.9653 | likely_pathogenic | 0.9826 | pathogenic | -3.204 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| P/F | 0.9495 | likely_pathogenic | 0.971 | pathogenic | -1.422 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| P/G | 0.8838 | likely_pathogenic | 0.9187 | pathogenic | -2.753 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| P/H | 0.9595 | likely_pathogenic | 0.9737 | pathogenic | -2.226 | Highly Destabilizing | 1.0 | D | 0.796 | deleterious | N | 0.479923479 | None | None | N |
| P/I | 0.4956 | ambiguous | 0.5464 | ambiguous | -1.129 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| P/K | 0.968 | likely_pathogenic | 0.9843 | pathogenic | -2.01 | Highly Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/L | 0.389 | ambiguous | 0.4334 | ambiguous | -1.129 | Destabilizing | 1.0 | D | 0.823 | deleterious | N | 0.475614157 | None | None | N |
| P/M | 0.7597 | likely_pathogenic | 0.8053 | pathogenic | -1.435 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| P/N | 0.9711 | likely_pathogenic | 0.9823 | pathogenic | -2.324 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| P/Q | 0.9116 | likely_pathogenic | 0.9465 | pathogenic | -2.303 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/R | 0.9236 | likely_pathogenic | 0.9611 | pathogenic | -1.636 | Destabilizing | 1.0 | D | 0.833 | deleterious | N | 0.479669989 | None | None | N |
| P/S | 0.7835 | likely_pathogenic | 0.8132 | pathogenic | -2.83 | Highly Destabilizing | 1.0 | D | 0.78 | deleterious | N | 0.47916301 | None | None | N |
| P/T | 0.5566 | ambiguous | 0.6034 | pathogenic | -2.556 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.478909521 | None | None | N |
| P/V | 0.3525 | ambiguous | 0.3707 | ambiguous | -1.502 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| P/W | 0.9923 | likely_pathogenic | 0.9962 | pathogenic | -1.813 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| P/Y | 0.9777 | likely_pathogenic | 0.989 | pathogenic | -1.546 | Destabilizing | 1.0 | D | 0.837 | 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.