Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23706 | 71341;71342;71343 | chr2:178575016;178575015;178575014 | chr2:179439743;179439742;179439741 |
| N2AB | 22065 | 66418;66419;66420 | chr2:178575016;178575015;178575014 | chr2:179439743;179439742;179439741 |
| N2A | 21138 | 63637;63638;63639 | chr2:178575016;178575015;178575014 | chr2:179439743;179439742;179439741 |
| N2B | 14641 | 44146;44147;44148 | chr2:178575016;178575015;178575014 | chr2:179439743;179439742;179439741 |
| Novex-1 | 14766 | 44521;44522;44523 | chr2:178575016;178575015;178575014 | chr2:179439743;179439742;179439741 |
| Novex-2 | 14833 | 44722;44723;44724 | chr2:178575016;178575015;178575014 | chr2:179439743;179439742;179439741 |
| 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/I | rs760319001  |
-0.734 | 0.016 | N | 0.409 | 0.052 | 0.107399877778 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.96181E-04 | None | 0 | 0 | 0 |
| L/I | rs760319001 |
-0.734 | 0.016 | N | 0.409 | 0.052 | 0.107399877778 | gnomAD-4.0.0 | 8.89672E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.50739E-04 | 0 |
| L/S | rs1481919740 |
-3.466 | 0.81 | N | 0.79 | 0.424 | 0.700159432204 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/S | rs1481919740 |
-3.466 | 0.81 | N | 0.79 | 0.424 | 0.700159432204 | gnomAD-4.0.0 | 1.59209E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43299E-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 | 0.7784 | likely_pathogenic | 0.8022 | pathogenic | -2.443 | Highly Destabilizing | 0.25 | N | 0.709 | prob.delet. | None | None | None | None | N |
| L/C | 0.7229 | likely_pathogenic | 0.7568 | pathogenic | -1.737 | Destabilizing | 0.992 | D | 0.779 | deleterious | None | None | None | None | N |
| L/D | 0.9981 | likely_pathogenic | 0.9981 | pathogenic | -2.439 | Highly Destabilizing | 0.972 | D | 0.846 | deleterious | None | None | None | None | N |
| L/E | 0.9856 | likely_pathogenic | 0.9866 | pathogenic | -2.25 | Highly Destabilizing | 0.92 | D | 0.833 | deleterious | None | None | None | None | N |
| L/F | 0.4093 | ambiguous | 0.4353 | ambiguous | -1.495 | Destabilizing | 0.81 | D | 0.692 | prob.neutral | N | 0.463769963 | None | None | N |
| L/G | 0.9716 | likely_pathogenic | 0.9751 | pathogenic | -2.973 | Highly Destabilizing | 0.92 | D | 0.812 | deleterious | None | None | None | None | N |
| L/H | 0.9627 | likely_pathogenic | 0.9644 | pathogenic | -2.379 | Highly Destabilizing | 0.992 | D | 0.857 | deleterious | None | None | None | None | N |
| L/I | 0.0823 | likely_benign | 0.0761 | benign | -0.933 | Destabilizing | 0.016 | N | 0.409 | neutral | N | 0.422730619 | None | None | N |
| L/K | 0.9743 | likely_pathogenic | 0.9761 | pathogenic | -1.864 | Destabilizing | 0.92 | D | 0.785 | deleterious | None | None | None | None | N |
| L/M | 0.1641 | likely_benign | 0.1877 | benign | -0.818 | Destabilizing | 0.059 | N | 0.42 | neutral | None | None | None | None | N |
| L/N | 0.984 | likely_pathogenic | 0.9861 | pathogenic | -2.051 | Highly Destabilizing | 0.972 | D | 0.843 | deleterious | None | None | None | None | N |
| L/P | 0.9755 | likely_pathogenic | 0.9764 | pathogenic | -1.414 | Destabilizing | 0.972 | D | 0.846 | deleterious | None | None | None | None | N |
| L/Q | 0.9386 | likely_pathogenic | 0.9468 | pathogenic | -1.968 | Destabilizing | 0.92 | D | 0.827 | deleterious | None | None | None | None | N |
| L/R | 0.9562 | likely_pathogenic | 0.9553 | pathogenic | -1.528 | Destabilizing | 0.92 | D | 0.827 | deleterious | None | None | None | None | N |
| L/S | 0.9652 | likely_pathogenic | 0.9691 | pathogenic | -2.787 | Highly Destabilizing | 0.81 | D | 0.79 | deleterious | N | 0.465290901 | None | None | N |
| L/T | 0.8519 | likely_pathogenic | 0.8662 | pathogenic | -2.447 | Highly Destabilizing | 0.617 | D | 0.729 | prob.delet. | None | None | None | None | N |
| L/V | 0.078 | likely_benign | 0.0742 | benign | -1.414 | Destabilizing | 0.002 | N | 0.396 | neutral | N | 0.380017204 | None | None | N |
| L/W | 0.9235 | likely_pathogenic | 0.9229 | pathogenic | -1.824 | Destabilizing | 0.992 | D | 0.833 | deleterious | None | None | None | None | N |
| L/Y | 0.9121 | likely_pathogenic | 0.9144 | pathogenic | -1.547 | Destabilizing | 0.92 | D | 0.774 | 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.