Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5376 | 16351;16352;16353 | chr2:178733050;178733049;178733048 | chr2:179597777;179597776;179597775 |
| N2AB | 5059 | 15400;15401;15402 | chr2:178733050;178733049;178733048 | chr2:179597777;179597776;179597775 |
| N2A | 4132 | 12619;12620;12621 | chr2:178733050;178733049;178733048 | chr2:179597777;179597776;179597775 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs72648936  |
-0.891 | 0.284 | D | 0.395 | 0.282 | None | gnomAD-2.1.1 | 5.01E-05 | None | None | None | None | N | None | 8.27E-05 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 8.03E-05 | 7.05E-05 | 0 |
| L/M | rs72648936 |
-0.891 | 0.284 | D | 0.395 | 0.282 | None | gnomAD-3.1.2 | 7.55793E-04 | None | None | None | None | N | None | 4.83E-05 | 0 | 1.11842E-01 | 0 | 0 | None | 9.42E-05 | 0 | 1.47007E-04 | 0 | 0 |
| L/M | rs72648936 |
-0.891 | 0.284 | D | 0.395 | 0.282 | None | gnomAD-4.0.0 | 1.16544E-04 | None | None | None | None | N | None | 2.66987E-05 | 1.6685E-05 | None | 0 | 2.23474E-05 | None | 4.68882E-05 | 0 | 6.5278E-05 | 0 | 3.20318E-05 |
| L/P | rs1560821110 |
None | 0.996 | D | 0.889 | 0.79 | 0.903425346708 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs1560821110 |
None | 0.996 | D | 0.889 | 0.79 | 0.903425346708 | gnomAD-4.0.0 | 6.57013E-06 | None | None | None | None | N | None | 2.4115E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7369 | likely_pathogenic | 0.7384 | pathogenic | -2.311 | Highly Destabilizing | 0.895 | D | 0.736 | prob.delet. | None | None | None | None | N |
| L/C | 0.8166 | likely_pathogenic | 0.8099 | pathogenic | -1.554 | Destabilizing | 0.999 | D | 0.8 | deleterious | None | None | None | None | N |
| L/D | 0.9931 | likely_pathogenic | 0.9933 | pathogenic | -2.794 | Highly Destabilizing | 0.997 | D | 0.893 | deleterious | None | None | None | None | N |
| L/E | 0.9559 | likely_pathogenic | 0.9557 | pathogenic | -2.515 | Highly Destabilizing | 0.992 | D | 0.889 | deleterious | None | None | None | None | N |
| L/F | 0.1037 | likely_benign | 0.0914 | benign | -1.389 | Destabilizing | 0.983 | D | 0.831 | deleterious | None | None | None | None | N |
| L/G | 0.9347 | likely_pathogenic | 0.9375 | pathogenic | -2.891 | Highly Destabilizing | 0.992 | D | 0.896 | deleterious | None | None | None | None | N |
| L/H | 0.8208 | likely_pathogenic | 0.8021 | pathogenic | -2.461 | Highly Destabilizing | 0.999 | D | 0.871 | deleterious | None | None | None | None | N |
| L/I | 0.16 | likely_benign | 0.1517 | benign | -0.603 | Destabilizing | 0.895 | D | 0.641 | neutral | None | None | None | None | N |
| L/K | 0.9283 | likely_pathogenic | 0.9259 | pathogenic | -1.653 | Destabilizing | 0.983 | D | 0.889 | deleterious | None | None | None | None | N |
| L/M | 0.1055 | likely_benign | 0.1052 | benign | -0.621 | Destabilizing | 0.284 | N | 0.395 | neutral | D | 0.558057316 | None | None | N |
| L/N | 0.9599 | likely_pathogenic | 0.9591 | pathogenic | -2.163 | Highly Destabilizing | 0.992 | D | 0.886 | deleterious | None | None | None | None | N |
| L/P | 0.9746 | likely_pathogenic | 0.9754 | pathogenic | -1.157 | Destabilizing | 0.996 | D | 0.889 | deleterious | D | 0.634025159 | None | None | N |
| L/Q | 0.7655 | likely_pathogenic | 0.7626 | pathogenic | -1.921 | Destabilizing | 0.989 | D | 0.87 | deleterious | D | 0.634025159 | None | None | N |
| L/R | 0.8651 | likely_pathogenic | 0.8646 | pathogenic | -1.632 | Destabilizing | 0.978 | D | 0.884 | deleterious | D | 0.634025159 | None | None | N |
| L/S | 0.9049 | likely_pathogenic | 0.9053 | pathogenic | -2.823 | Highly Destabilizing | 0.983 | D | 0.887 | deleterious | None | None | None | None | N |
| L/T | 0.8135 | likely_pathogenic | 0.8136 | pathogenic | -2.377 | Highly Destabilizing | 0.983 | D | 0.834 | deleterious | None | None | None | None | N |
| L/V | 0.1962 | likely_benign | 0.1932 | benign | -1.157 | Destabilizing | 0.865 | D | 0.688 | prob.neutral | D | 0.58472589 | None | None | N |
| L/W | 0.4623 | ambiguous | 0.4447 | ambiguous | -1.791 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | N |
| L/Y | 0.6256 | likely_pathogenic | 0.5865 | pathogenic | -1.456 | Destabilizing | 0.992 | D | 0.818 | 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.