Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27802 | 83629;83630;83631 | chr2:178562728;178562727;178562726 | chr2:179427455;179427454;179427453 |
| N2AB | 26161 | 78706;78707;78708 | chr2:178562728;178562727;178562726 | chr2:179427455;179427454;179427453 |
| N2A | 25234 | 75925;75926;75927 | chr2:178562728;178562727;178562726 | chr2:179427455;179427454;179427453 |
| N2B | 18737 | 56434;56435;56436 | chr2:178562728;178562727;178562726 | chr2:179427455;179427454;179427453 |
| Novex-1 | 18862 | 56809;56810;56811 | chr2:178562728;178562727;178562726 | chr2:179427455;179427454;179427453 |
| Novex-2 | 18929 | 57010;57011;57012 | chr2:178562728;178562727;178562726 | chr2:179427455;179427454;179427453 |
| 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/T | rs887481991  |
-2.73 | 0.984 | N | 0.611 | 0.418 | 0.691580264319 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| I/T | rs887481991 |
-2.73 | 0.984 | N | 0.611 | 0.418 | 0.691580264319 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs887481991 |
-2.73 | 0.984 | N | 0.611 | 0.418 | 0.691580264319 | gnomAD-4.0.0 | 3.87894E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.23795E-06 | 0 | 0 |
| I/V | rs727504723 |
-1.705 | 0.011 | N | 0.27 | 0.06 | 0.36076525451 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| I/V | rs727504723 |
-1.705 | 0.011 | N | 0.27 | 0.06 | 0.36076525451 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs727504723 |
-1.705 | 0.011 | N | 0.27 | 0.06 | 0.36076525451 | gnomAD-4.0.0 | 1.30687E-05 | None | None | None | None | N | None | 2.68579E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.53002E-05 | 0 | 1.61077E-05 |
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 | 0.5095 | ambiguous | 0.5583 | ambiguous | -2.503 | Highly Destabilizing | 0.993 | D | 0.551 | neutral | None | None | None | None | N |
| I/C | 0.7592 | likely_pathogenic | 0.7766 | pathogenic | -2.064 | Highly Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/D | 0.9617 | likely_pathogenic | 0.9634 | pathogenic | -2.926 | Highly Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/E | 0.9011 | likely_pathogenic | 0.8989 | pathogenic | -2.803 | Highly Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/F | 0.3121 | likely_benign | 0.3257 | benign | -1.628 | Destabilizing | 0.998 | D | 0.672 | neutral | N | 0.479825028 | None | None | N |
| I/G | 0.9138 | likely_pathogenic | 0.9163 | pathogenic | -2.947 | Highly Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/H | 0.717 | likely_pathogenic | 0.7275 | pathogenic | -2.164 | Highly Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/K | 0.7681 | likely_pathogenic | 0.7794 | pathogenic | -1.874 | Destabilizing | 0.983 | D | 0.718 | prob.delet. | None | None | None | None | N |
| I/L | 0.206 | likely_benign | 0.1993 | benign | -1.261 | Destabilizing | 0.359 | N | 0.423 | neutral | N | 0.49063884 | None | None | N |
| I/M | 0.1613 | likely_benign | 0.1736 | benign | -1.251 | Destabilizing | 0.994 | D | 0.683 | prob.neutral | N | 0.496385573 | None | None | N |
| I/N | 0.6635 | likely_pathogenic | 0.6679 | pathogenic | -2.047 | Highly Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.472125572 | None | None | N |
| I/P | 0.992 | likely_pathogenic | 0.9926 | pathogenic | -1.653 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| I/Q | 0.7611 | likely_pathogenic | 0.7629 | pathogenic | -2.114 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/R | 0.6393 | likely_pathogenic | 0.657 | pathogenic | -1.341 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| I/S | 0.5331 | ambiguous | 0.5643 | pathogenic | -2.701 | Highly Destabilizing | 0.999 | D | 0.649 | neutral | N | 0.471516461 | None | None | N |
| I/T | 0.2103 | likely_benign | 0.2518 | benign | -2.452 | Highly Destabilizing | 0.984 | D | 0.611 | neutral | N | 0.51911352 | None | None | N |
| I/V | 0.0693 | likely_benign | 0.0735 | benign | -1.653 | Destabilizing | 0.011 | N | 0.27 | neutral | N | 0.455430188 | None | None | N |
| I/W | 0.8915 | likely_pathogenic | 0.8994 | pathogenic | -1.88 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/Y | 0.723 | likely_pathogenic | 0.7351 | pathogenic | -1.657 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | 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.