Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22570 | 67933;67934;67935 | chr2:178579322;178579321;178579320 | chr2:179444049;179444048;179444047 |
| N2AB | 20929 | 63010;63011;63012 | chr2:178579322;178579321;178579320 | chr2:179444049;179444048;179444047 |
| N2A | 20002 | 60229;60230;60231 | chr2:178579322;178579321;178579320 | chr2:179444049;179444048;179444047 |
| N2B | 13505 | 40738;40739;40740 | chr2:178579322;178579321;178579320 | chr2:179444049;179444048;179444047 |
| Novex-1 | 13630 | 41113;41114;41115 | chr2:178579322;178579321;178579320 | chr2:179444049;179444048;179444047 |
| Novex-2 | 13697 | 41314;41315;41316 | chr2:178579322;178579321;178579320 | chr2:179444049;179444048;179444047 |
| 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/F | rs1198941645  |
-1.243 | 0.982 | D | 0.713 | 0.326 | 0.552326942858 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| L/F | rs1198941645 |
-1.243 | 0.982 | D | 0.713 | 0.326 | 0.552326942858 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs1198941645 |
-1.243 | 0.982 | D | 0.713 | 0.326 | 0.552326942858 | gnomAD-4.0.0 | 6.57756E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47124E-05 | 0 | 0 |
| L/V | rs1198941645 |
None | 0.76 | D | 0.592 | 0.428 | 0.535102873643 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| L/V | rs1198941645 |
None | 0.76 | D | 0.592 | 0.428 | 0.535102873643 | gnomAD-4.0.0 | 1.60501E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88218E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9125 | likely_pathogenic | 0.911 | pathogenic | -1.911 | Destabilizing | 0.953 | D | 0.656 | neutral | None | None | None | None | I |
| L/C | 0.8563 | likely_pathogenic | 0.8548 | pathogenic | -1.292 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | I |
| L/D | 0.9985 | likely_pathogenic | 0.9983 | pathogenic | -1.896 | Destabilizing | 0.998 | D | 0.819 | deleterious | None | None | None | None | I |
| L/E | 0.9889 | likely_pathogenic | 0.9863 | pathogenic | -1.653 | Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | I |
| L/F | 0.433 | ambiguous | 0.4021 | ambiguous | -1.186 | Destabilizing | 0.982 | D | 0.713 | prob.delet. | D | 0.52284255 | None | None | I |
| L/G | 0.9827 | likely_pathogenic | 0.9816 | pathogenic | -2.39 | Highly Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | I |
| L/H | 0.9665 | likely_pathogenic | 0.9605 | pathogenic | -1.774 | Destabilizing | 0.999 | D | 0.81 | deleterious | D | 0.601289943 | None | None | I |
| L/I | 0.1161 | likely_benign | 0.1139 | benign | -0.518 | Destabilizing | 0.046 | N | 0.27 | neutral | N | 0.518954187 | None | None | I |
| L/K | 0.9789 | likely_pathogenic | 0.9712 | pathogenic | -1.353 | Destabilizing | 0.993 | D | 0.809 | deleterious | None | None | None | None | I |
| L/M | 0.2275 | likely_benign | 0.2189 | benign | -0.617 | Destabilizing | 0.986 | D | 0.654 | neutral | None | None | None | None | I |
| L/N | 0.992 | likely_pathogenic | 0.9906 | pathogenic | -1.834 | Destabilizing | 0.998 | D | 0.827 | deleterious | None | None | None | None | I |
| L/P | 0.9916 | likely_pathogenic | 0.9892 | pathogenic | -0.967 | Destabilizing | 0.997 | D | 0.823 | deleterious | D | 0.601289943 | None | None | I |
| L/Q | 0.951 | likely_pathogenic | 0.9384 | pathogenic | -1.571 | Destabilizing | 0.998 | D | 0.817 | deleterious | None | None | None | None | I |
| L/R | 0.9653 | likely_pathogenic | 0.9565 | pathogenic | -1.388 | Destabilizing | 0.997 | D | 0.8 | deleterious | D | 0.601289943 | None | None | I |
| L/S | 0.9878 | likely_pathogenic | 0.9871 | pathogenic | -2.47 | Highly Destabilizing | 0.993 | D | 0.807 | deleterious | None | None | None | None | I |
| L/T | 0.9549 | likely_pathogenic | 0.9534 | pathogenic | -2.067 | Highly Destabilizing | 0.986 | D | 0.721 | prob.delet. | None | None | None | None | I |
| L/V | 0.1648 | likely_benign | 0.1641 | benign | -0.967 | Destabilizing | 0.76 | D | 0.592 | neutral | D | 0.561939827 | None | None | I |
| L/W | 0.8444 | likely_pathogenic | 0.8237 | pathogenic | -1.402 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | I |
| L/Y | 0.8852 | likely_pathogenic | 0.8701 | pathogenic | -1.116 | Destabilizing | 0.998 | D | 0.702 | prob.neutral | None | None | None | None | I |
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.