Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32973 | 99142;99143;99144 | chr2:178539018;178539017;178539016 | chr2:179403745;179403744;179403743 |
| N2AB | 31332 | 94219;94220;94221 | chr2:178539018;178539017;178539016 | chr2:179403745;179403744;179403743 |
| N2A | 30405 | 91438;91439;91440 | chr2:178539018;178539017;178539016 | chr2:179403745;179403744;179403743 |
| N2B | 23908 | 71947;71948;71949 | chr2:178539018;178539017;178539016 | chr2:179403745;179403744;179403743 |
| Novex-1 | 24033 | 72322;72323;72324 | chr2:178539018;178539017;178539016 | chr2:179403745;179403744;179403743 |
| Novex-2 | 24100 | 72523;72524;72525 | chr2:178539018;178539017;178539016 | chr2:179403745;179403744;179403743 |
| 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/S | None | None | 0.891 | N | 0.725 | 0.375 | 0.704728438482 | gnomAD-4.0.0 | 1.59141E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88239E-05 | 0 | 0 | 0 | 0 |
| I/V | rs773080115  |
-1.806 | 0.002 | N | 0.244 | 0.07 | None | 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 |
| I/V | rs773080115 |
-1.806 | 0.002 | N | 0.244 | 0.07 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs773080115 |
-1.806 | 0.002 | N | 0.244 | 0.07 | None | gnomAD-4.0.0 | 3.09852E-06 | None | None | None | None | N | None | 5.33903E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47646E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3992 | ambiguous | 0.3998 | ambiguous | -2.784 | Highly Destabilizing | 0.525 | D | 0.653 | neutral | None | None | None | None | N |
| I/C | 0.7231 | likely_pathogenic | 0.7345 | pathogenic | -1.986 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/D | 0.9474 | likely_pathogenic | 0.9292 | pathogenic | -3.217 | Highly Destabilizing | 0.991 | D | 0.762 | deleterious | None | None | None | None | N |
| I/E | 0.8502 | likely_pathogenic | 0.8191 | pathogenic | -2.994 | Highly Destabilizing | 0.974 | D | 0.753 | deleterious | None | None | None | None | N |
| I/F | 0.2346 | likely_benign | 0.2087 | benign | -1.586 | Destabilizing | 0.934 | D | 0.733 | prob.delet. | N | 0.409967257 | None | None | N |
| I/G | 0.8499 | likely_pathogenic | 0.8507 | pathogenic | -3.284 | Highly Destabilizing | 0.974 | D | 0.757 | deleterious | None | None | None | None | N |
| I/H | 0.6991 | likely_pathogenic | 0.6589 | pathogenic | -2.664 | Highly Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | N |
| I/K | 0.6916 | likely_pathogenic | 0.6087 | pathogenic | -2.068 | Highly Destabilizing | 0.974 | D | 0.755 | deleterious | None | None | None | None | N |
| I/L | 0.1662 | likely_benign | 0.1597 | benign | -1.318 | Destabilizing | 0.005 | N | 0.275 | neutral | N | 0.444559833 | None | None | N |
| I/M | 0.1255 | likely_benign | 0.1188 | benign | -1.389 | Destabilizing | 0.973 | D | 0.717 | prob.delet. | N | 0.443349112 | None | None | N |
| I/N | 0.6123 | likely_pathogenic | 0.5614 | ambiguous | -2.427 | Highly Destabilizing | 0.989 | D | 0.764 | deleterious | N | 0.509726033 | None | None | N |
| I/P | 0.991 | likely_pathogenic | 0.9891 | pathogenic | -1.792 | Destabilizing | 0.991 | D | 0.759 | deleterious | None | None | None | None | N |
| I/Q | 0.6355 | likely_pathogenic | 0.6013 | pathogenic | -2.293 | Highly Destabilizing | 0.991 | D | 0.758 | deleterious | None | None | None | None | N |
| I/R | 0.5584 | ambiguous | 0.4819 | ambiguous | -1.746 | Destabilizing | 0.974 | D | 0.767 | deleterious | None | None | None | None | N |
| I/S | 0.4109 | ambiguous | 0.3986 | ambiguous | -3.044 | Highly Destabilizing | 0.891 | D | 0.725 | prob.delet. | N | 0.423723201 | None | None | N |
| I/T | 0.2142 | likely_benign | 0.2016 | benign | -2.696 | Highly Destabilizing | 0.801 | D | 0.695 | prob.neutral | N | 0.443231682 | None | None | N |
| I/V | 0.0968 | likely_benign | 0.0971 | benign | -1.792 | Destabilizing | 0.002 | N | 0.244 | neutral | N | 0.394381729 | None | None | N |
| I/W | 0.868 | likely_pathogenic | 0.8482 | pathogenic | -1.962 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Y | 0.6618 | likely_pathogenic | 0.6243 | pathogenic | -1.758 | Destabilizing | 0.974 | D | 0.758 | 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.