Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22691 | 68296;68297;68298 | chr2:178578959;178578958;178578957 | chr2:179443686;179443685;179443684 |
| N2AB | 21050 | 63373;63374;63375 | chr2:178578959;178578958;178578957 | chr2:179443686;179443685;179443684 |
| N2A | 20123 | 60592;60593;60594 | chr2:178578959;178578958;178578957 | chr2:179443686;179443685;179443684 |
| N2B | 13626 | 41101;41102;41103 | chr2:178578959;178578958;178578957 | chr2:179443686;179443685;179443684 |
| Novex-1 | 13751 | 41476;41477;41478 | chr2:178578959;178578958;178578957 | chr2:179443686;179443685;179443684 |
| Novex-2 | 13818 | 41677;41678;41679 | chr2:178578959;178578958;178578957 | chr2:179443686;179443685;179443684 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/R | rs565422738  |
-0.747 | 1.0 | D | 0.753 | 0.607 | 0.743538347216 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| W/R | rs565422738 |
-0.747 | 1.0 | D | 0.753 | 0.607 | 0.743538347216 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| W/R | rs565422738 |
-0.747 | 1.0 | D | 0.753 | 0.607 | 0.743538347216 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| W/R | rs565422738 |
-0.747 | 1.0 | D | 0.753 | 0.607 | 0.743538347216 | gnomAD-4.0.0 | 1.59237E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86028E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9946 | likely_pathogenic | 0.9943 | pathogenic | -3.119 | Highly Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| W/C | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -1.327 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.488387084 | None | None | N |
| W/D | 0.998 | likely_pathogenic | 0.998 | pathogenic | -1.603 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| W/E | 0.9988 | likely_pathogenic | 0.9989 | pathogenic | -1.541 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| W/F | 0.826 | likely_pathogenic | 0.8291 | pathogenic | -2.019 | Highly Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| W/G | 0.9843 | likely_pathogenic | 0.9828 | pathogenic | -3.311 | Highly Destabilizing | 1.0 | D | 0.7 | prob.neutral | D | 0.525227477 | None | None | N |
| W/H | 0.996 | likely_pathogenic | 0.9963 | pathogenic | -1.587 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| W/I | 0.9927 | likely_pathogenic | 0.9922 | pathogenic | -2.424 | Highly Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| W/K | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.591 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| W/L | 0.9791 | likely_pathogenic | 0.9776 | pathogenic | -2.424 | Highly Destabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.513110703 | None | None | N |
| W/M | 0.9926 | likely_pathogenic | 0.9926 | pathogenic | -1.812 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| W/N | 0.998 | likely_pathogenic | 0.9981 | pathogenic | -1.847 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| W/P | 0.9964 | likely_pathogenic | 0.9966 | pathogenic | -2.671 | Highly Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| W/Q | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.896 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| W/R | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -0.916 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.525734456 | None | None | N |
| W/S | 0.9924 | likely_pathogenic | 0.9924 | pathogenic | -2.333 | Highly Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.52370654 | None | None | N |
| W/T | 0.9947 | likely_pathogenic | 0.9946 | pathogenic | -2.228 | Highly Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| W/V | 0.992 | likely_pathogenic | 0.9916 | pathogenic | -2.671 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| W/Y | 0.9206 | likely_pathogenic | 0.9222 | pathogenic | -1.83 | Destabilizing | 1.0 | D | 0.606 | 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.