Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
| N2AB | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
| N2A | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
| N2B | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
| Novex-1 | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
| Novex-2 | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
| Novex-3 | 158 | 697;698;699 | chr2:178800506;178800505;178800504 | chr2:179665233;179665232;179665231 |
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 | rs1490704308  |
-1.503 | 0.374 | N | 0.306 | 0.236 | 0.479208069955 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | -0.319(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| L/F | rs1490704308 |
-1.503 | 0.374 | N | 0.306 | 0.236 | 0.479208069955 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.319(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs1490704308 |
-1.503 | 0.374 | N | 0.306 | 0.236 | 0.479208069955 | gnomAD-4.0.0 | 1.85869E-06 | None | None | None | -0.319(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54231E-06 | 0 | 0 |
| L/V | None | None | 0.097 | N | 0.343 | 0.232 | 0.393159880135 | gnomAD-4.0.0 | 6.84056E-07 | None | None | None | -0.384(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9929E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3564 | ambiguous | 0.4014 | ambiguous | -2.226 | Highly Destabilizing | 0.996 | D | 0.566 | neutral | None | None | None | -0.136(TCAP) | N |
| L/C | 0.7841 | likely_pathogenic | 0.82 | pathogenic | -1.508 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | -1.066(TCAP) | N |
| L/D | 0.6776 | likely_pathogenic | 0.7261 | pathogenic | -2.149 | Highly Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | -1.068(TCAP) | N |
| L/E | 0.3987 | ambiguous | 0.4505 | ambiguous | -2.073 | Highly Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | -1.256(TCAP) | N |
| L/F | 0.2249 | likely_benign | 0.2495 | benign | -1.507 | Destabilizing | 0.374 | N | 0.306 | neutral | N | 0.47101159 | None | -0.319(TCAP) | N |
| L/G | 0.7097 | likely_pathogenic | 0.7578 | pathogenic | -2.618 | Highly Destabilizing | 0.999 | D | 0.764 | deleterious | None | None | None | -0.035(TCAP) | N |
| L/H | 0.3344 | likely_benign | 0.3825 | ambiguous | -1.794 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.493141674 | None | -0.105(TCAP) | N |
| L/I | 0.0994 | likely_benign | 0.1029 | benign | -1.162 | Destabilizing | 0.753 | D | 0.452 | neutral | N | 0.428831408 | None | -0.529(TCAP) | N |
| L/K | 0.3674 | ambiguous | 0.4037 | ambiguous | -1.483 | Destabilizing | 0.994 | D | 0.76 | deleterious | None | None | None | -1.336(TCAP) | N |
| L/M | 0.1672 | likely_benign | 0.1742 | benign | -1.008 | Destabilizing | 0.996 | D | 0.682 | prob.neutral | None | None | None | -0.739(TCAP) | N |
| L/N | 0.4201 | ambiguous | 0.4642 | ambiguous | -1.475 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | -0.812(TCAP) | N |
| L/P | 0.9468 | likely_pathogenic | 0.9551 | pathogenic | -1.491 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.504588729 | None | -0.384(TCAP) | N |
| L/Q | 0.2104 | likely_benign | 0.2423 | benign | -1.614 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | -0.912(TCAP) | N |
| L/R | 0.2464 | likely_benign | 0.2894 | benign | -0.916 | Destabilizing | 0.999 | D | 0.767 | deleterious | N | 0.41367905 | None | -1.501(TCAP) | N |
| L/S | 0.3713 | ambiguous | 0.4331 | ambiguous | -2.138 | Highly Destabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | -0.455(TCAP) | N |
| L/T | 0.2076 | likely_benign | 0.2324 | benign | -1.946 | Destabilizing | 0.997 | D | 0.686 | prob.neutral | None | None | None | -0.639(TCAP) | N |
| L/V | 0.1061 | likely_benign | 0.1092 | benign | -1.491 | Destabilizing | 0.097 | N | 0.343 | neutral | N | 0.390541797 | None | -0.384(TCAP) | N |
| L/W | 0.461 | ambiguous | 0.5109 | ambiguous | -1.665 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | -0.679(TCAP) | N |
| L/Y | 0.5031 | ambiguous | 0.5391 | ambiguous | -1.435 | Destabilizing | 0.957 | D | 0.755 | deleterious | None | None | None | -0.369(TCAP) | 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.