Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23385 | 70378;70379;70380 | chr2:178575979;178575978;178575977 | chr2:179440706;179440705;179440704 |
| N2AB | 21744 | 65455;65456;65457 | chr2:178575979;178575978;178575977 | chr2:179440706;179440705;179440704 |
| N2A | 20817 | 62674;62675;62676 | chr2:178575979;178575978;178575977 | chr2:179440706;179440705;179440704 |
| N2B | 14320 | 43183;43184;43185 | chr2:178575979;178575978;178575977 | chr2:179440706;179440705;179440704 |
| Novex-1 | 14445 | 43558;43559;43560 | chr2:178575979;178575978;178575977 | chr2:179440706;179440705;179440704 |
| Novex-2 | 14512 | 43759;43760;43761 | chr2:178575979;178575978;178575977 | chr2:179440706;179440705;179440704 |
| 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/M | rs769672151  |
-0.86 | 0.999 | N | 0.724 | 0.443 | 0.747100778764 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66003E-04 |
| L/M | rs769672151 |
-0.86 | 0.999 | N | 0.724 | 0.443 | 0.747100778764 | gnomAD-4.0.0 | 6.85221E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00847E-07 | 0 | 0 |
| L/P | rs747995899 |
-0.95 | 1.0 | D | 0.795 | 0.829 | 0.897133140693 | 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/P | rs747995899 |
-0.95 | 1.0 | D | 0.795 | 0.829 | 0.897133140693 | gnomAD-4.0.0 | 2.74122E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.64188E-05 | 0 |
| L/V | rs769672151 |
-1.062 | 0.981 | N | 0.53 | 0.354 | 0.567569374525 | 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/V | rs769672151 |
-1.062 | 0.981 | N | 0.53 | 0.354 | 0.567569374525 | gnomAD-4.0.0 | 1.37044E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.3204E-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 | 0.8645 | likely_pathogenic | 0.882 | pathogenic | -2.487 | Highly Destabilizing | 0.998 | D | 0.603 | neutral | None | None | None | None | N |
| L/C | 0.8934 | likely_pathogenic | 0.9106 | pathogenic | -2.009 | Highly Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/D | 0.9898 | likely_pathogenic | 0.9915 | pathogenic | -2.249 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/E | 0.9615 | likely_pathogenic | 0.9664 | pathogenic | -2.02 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| L/F | 0.5743 | likely_pathogenic | 0.6021 | pathogenic | -1.495 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| L/G | 0.9627 | likely_pathogenic | 0.9673 | pathogenic | -3.048 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| L/H | 0.9428 | likely_pathogenic | 0.9526 | pathogenic | -2.384 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/I | 0.1571 | likely_benign | 0.1555 | benign | -0.876 | Destabilizing | 0.91 | D | 0.345 | neutral | None | None | None | None | N |
| L/K | 0.9555 | likely_pathogenic | 0.9593 | pathogenic | -1.999 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| L/M | 0.2739 | likely_benign | 0.2781 | benign | -0.888 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | N | 0.499048368 | None | None | N |
| L/N | 0.9574 | likely_pathogenic | 0.9629 | pathogenic | -2.323 | Highly Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| L/P | 0.8252 | likely_pathogenic | 0.8499 | pathogenic | -1.391 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.528206213 | None | None | N |
| L/Q | 0.9072 | likely_pathogenic | 0.9178 | pathogenic | -2.139 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.517103398 | None | None | N |
| L/R | 0.9374 | likely_pathogenic | 0.9433 | pathogenic | -1.762 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.521458264 | None | None | N |
| L/S | 0.9559 | likely_pathogenic | 0.964 | pathogenic | -3.125 | Highly Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| L/T | 0.8278 | likely_pathogenic | 0.8446 | pathogenic | -2.724 | Highly Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| L/V | 0.1897 | likely_benign | 0.2029 | benign | -1.391 | Destabilizing | 0.981 | D | 0.53 | neutral | N | 0.494160013 | None | None | N |
| L/W | 0.8576 | likely_pathogenic | 0.879 | pathogenic | -1.761 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/Y | 0.9109 | likely_pathogenic | 0.9186 | pathogenic | -1.498 | Destabilizing | 1.0 | D | 0.77 | 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.