Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30267 | 91024;91025;91026 | chr2:178552101;178552100;178552099 | chr2:179416828;179416827;179416826 |
| N2AB | 28626 | 86101;86102;86103 | chr2:178552101;178552100;178552099 | chr2:179416828;179416827;179416826 |
| N2A | 27699 | 83320;83321;83322 | chr2:178552101;178552100;178552099 | chr2:179416828;179416827;179416826 |
| N2B | 21202 | 63829;63830;63831 | chr2:178552101;178552100;178552099 | chr2:179416828;179416827;179416826 |
| Novex-1 | 21327 | 64204;64205;64206 | chr2:178552101;178552100;178552099 | chr2:179416828;179416827;179416826 |
| Novex-2 | 21394 | 64405;64406;64407 | chr2:178552101;178552100;178552099 | chr2:179416828;179416827;179416826 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs377365979  |
-1.101 | None | N | 0.157 | 0.06 | None | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.68E-05 | 0 |
| T/A | rs377365979 |
-1.101 | None | N | 0.157 | 0.06 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/A | rs377365979 |
-1.101 | None | N | 0.157 | 0.06 | None | gnomAD-4.0.0 | 5.5774E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62859E-06 | 0 | 0 |
| T/N | None | None | 0.117 | N | 0.389 | 0.284 | 0.254244900254 | gnomAD-4.0.0 | 1.59141E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77346E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0644 | likely_benign | 0.0691 | benign | -0.802 | Destabilizing | None | N | 0.157 | neutral | N | 0.488542684 | None | None | N |
| T/C | 0.4262 | ambiguous | 0.4416 | ambiguous | -0.516 | Destabilizing | 0.824 | D | 0.433 | neutral | None | None | None | None | N |
| T/D | 0.506 | ambiguous | 0.4404 | ambiguous | -0.131 | Destabilizing | 0.149 | N | 0.413 | neutral | None | None | None | None | N |
| T/E | 0.4078 | ambiguous | 0.3758 | ambiguous | -0.147 | Destabilizing | 0.149 | N | 0.348 | neutral | None | None | None | None | N |
| T/F | 0.387 | ambiguous | 0.3404 | ambiguous | -0.87 | Destabilizing | 0.555 | D | 0.535 | neutral | None | None | None | None | N |
| T/G | 0.2304 | likely_benign | 0.2228 | benign | -1.043 | Destabilizing | 0.035 | N | 0.444 | neutral | None | None | None | None | N |
| T/H | 0.3974 | ambiguous | 0.3677 | ambiguous | -1.25 | Destabilizing | 0.935 | D | 0.519 | neutral | None | None | None | None | N |
| T/I | 0.1925 | likely_benign | 0.1694 | benign | -0.256 | Destabilizing | 0.317 | N | 0.41 | neutral | N | 0.468672986 | None | None | N |
| T/K | 0.342 | ambiguous | 0.2785 | benign | -0.74 | Destabilizing | 0.149 | N | 0.362 | neutral | None | None | None | None | N |
| T/L | 0.141 | likely_benign | 0.1309 | benign | -0.256 | Destabilizing | 0.081 | N | 0.345 | neutral | None | None | None | None | N |
| T/M | 0.1099 | likely_benign | 0.1011 | benign | 0.028 | Stabilizing | 0.555 | D | 0.437 | neutral | None | None | None | None | N |
| T/N | 0.1539 | likely_benign | 0.1272 | benign | -0.6 | Destabilizing | 0.117 | N | 0.389 | neutral | N | 0.505821723 | None | None | N |
| T/P | 0.1944 | likely_benign | 0.1742 | benign | -0.406 | Destabilizing | 0.317 | N | 0.429 | neutral | N | 0.511035541 | None | None | N |
| T/Q | 0.3127 | likely_benign | 0.2992 | benign | -0.811 | Destabilizing | 0.38 | N | 0.458 | neutral | None | None | None | None | N |
| T/R | 0.3363 | likely_benign | 0.2799 | benign | -0.441 | Destabilizing | 0.38 | N | 0.433 | neutral | None | None | None | None | N |
| T/S | 0.1157 | likely_benign | 0.1098 | benign | -0.911 | Destabilizing | 0.001 | N | 0.149 | neutral | N | 0.482790147 | None | None | N |
| T/V | 0.1401 | likely_benign | 0.13 | benign | -0.406 | Destabilizing | 0.081 | N | 0.318 | neutral | None | None | None | None | N |
| T/W | 0.7622 | likely_pathogenic | 0.7364 | pathogenic | -0.765 | Destabilizing | 0.935 | D | 0.579 | neutral | None | None | None | None | N |
| T/Y | 0.3944 | ambiguous | 0.3644 | ambiguous | -0.556 | Destabilizing | 0.555 | D | 0.539 | 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.