Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19355 | 58288;58289;58290 | chr2:178594431;178594430;178594429 | chr2:179459158;179459157;179459156 |
| N2AB | 17714 | 53365;53366;53367 | chr2:178594431;178594430;178594429 | chr2:179459158;179459157;179459156 |
| N2A | 16787 | 50584;50585;50586 | chr2:178594431;178594430;178594429 | chr2:179459158;179459157;179459156 |
| N2B | 10290 | 31093;31094;31095 | chr2:178594431;178594430;178594429 | chr2:179459158;179459157;179459156 |
| Novex-1 | 10415 | 31468;31469;31470 | chr2:178594431;178594430;178594429 | chr2:179459158;179459157;179459156 |
| Novex-2 | 10482 | 31669;31670;31671 | chr2:178594431;178594430;178594429 | chr2:179459158;179459157;179459156 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs766593902  |
-1.884 | 1.0 | D | 0.823 | 0.835 | 0.932893900741 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Y/C | rs766593902 |
-1.884 | 1.0 | D | 0.823 | 0.835 | 0.932893900741 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs766593902 |
-1.884 | 1.0 | D | 0.823 | 0.835 | 0.932893900741 | gnomAD-4.0.0 | 9.92088E-06 | None | None | None | None | N | None | 0 | 3.33868E-05 | None | 0 | 0 | None | 0 | 0 | 1.10229E-05 | 1.10011E-05 | 0 |
| Y/F | None | None | 0.994 | D | 0.704 | 0.748 | 0.789998404534 | gnomAD-4.0.0 | 6.84634E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99798E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9568 | likely_pathogenic | 0.9382 | pathogenic | -2.91 | Highly Destabilizing | 0.996 | D | 0.801 | deleterious | None | None | None | None | N |
| Y/C | 0.5564 | ambiguous | 0.501 | ambiguous | -1.648 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.676418364 | None | None | N |
| Y/D | 0.9846 | likely_pathogenic | 0.9783 | pathogenic | -3.101 | Highly Destabilizing | 0.998 | D | 0.842 | deleterious | D | 0.676418364 | None | None | N |
| Y/E | 0.9883 | likely_pathogenic | 0.9825 | pathogenic | -2.895 | Highly Destabilizing | 0.998 | D | 0.768 | deleterious | None | None | None | None | N |
| Y/F | 0.1179 | likely_benign | 0.1111 | benign | -0.988 | Destabilizing | 0.994 | D | 0.704 | prob.neutral | D | 0.594040992 | None | None | N |
| Y/G | 0.9669 | likely_pathogenic | 0.95 | pathogenic | -3.332 | Highly Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| Y/H | 0.6408 | likely_pathogenic | 0.5708 | pathogenic | -1.938 | Destabilizing | 0.217 | N | 0.498 | neutral | D | 0.644147478 | None | None | N |
| Y/I | 0.8793 | likely_pathogenic | 0.8471 | pathogenic | -1.52 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| Y/K | 0.9768 | likely_pathogenic | 0.9665 | pathogenic | -2.007 | Highly Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| Y/L | 0.8097 | likely_pathogenic | 0.7887 | pathogenic | -1.52 | Destabilizing | 0.996 | D | 0.76 | deleterious | None | None | None | None | N |
| Y/M | 0.8904 | likely_pathogenic | 0.8743 | pathogenic | -1.282 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| Y/N | 0.8861 | likely_pathogenic | 0.8442 | pathogenic | -2.772 | Highly Destabilizing | 0.997 | D | 0.797 | deleterious | D | 0.67621656 | None | None | N |
| Y/P | 0.9983 | likely_pathogenic | 0.9973 | pathogenic | -1.997 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| Y/Q | 0.9653 | likely_pathogenic | 0.9484 | pathogenic | -2.52 | Highly Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| Y/R | 0.9257 | likely_pathogenic | 0.8953 | pathogenic | -1.786 | Destabilizing | 0.998 | D | 0.817 | deleterious | None | None | None | None | N |
| Y/S | 0.8983 | likely_pathogenic | 0.8532 | pathogenic | -3.157 | Highly Destabilizing | 0.998 | D | 0.771 | deleterious | D | 0.660399003 | None | None | N |
| Y/T | 0.9569 | likely_pathogenic | 0.9352 | pathogenic | -2.83 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| Y/V | 0.7856 | likely_pathogenic | 0.7322 | pathogenic | -1.997 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| Y/W | 0.5058 | ambiguous | 0.4549 | ambiguous | -0.323 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | 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.