Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28586 | 85981;85982;85983 | chr2:178560376;178560375;178560374 | chr2:179425103;179425102;179425101 |
| N2AB | 26945 | 81058;81059;81060 | chr2:178560376;178560375;178560374 | chr2:179425103;179425102;179425101 |
| N2A | 26018 | 78277;78278;78279 | chr2:178560376;178560375;178560374 | chr2:179425103;179425102;179425101 |
| N2B | 19521 | 58786;58787;58788 | chr2:178560376;178560375;178560374 | chr2:179425103;179425102;179425101 |
| Novex-1 | 19646 | 59161;59162;59163 | chr2:178560376;178560375;178560374 | chr2:179425103;179425102;179425101 |
| Novex-2 | 19713 | 59362;59363;59364 | chr2:178560376;178560375;178560374 | chr2:179425103;179425102;179425101 |
| 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/K | rs773336002  |
-2.549 | 0.773 | N | 0.731 | 0.372 | 0.72415221971 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/K | rs773336002 |
-2.549 | 0.773 | N | 0.731 | 0.372 | 0.72415221971 | 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 |
| I/K | rs773336002 |
-2.549 | 0.773 | N | 0.731 | 0.372 | 0.72415221971 | gnomAD-4.0.0 | 3.04486E-06 | None | None | None | None | N | None | 5.24146E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | None | None | 0.001 | N | 0.259 | 0.086 | 0.377799810692 | gnomAD-4.0.0 | 3.42126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49738E-06 | 0 | 0 |
| I/V | rs1187128207 |
None | None | N | 0.202 | 0.072 | 0.312306559268 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1187128207 |
None | None | N | 0.202 | 0.072 | 0.312306559268 | gnomAD-4.0.0 | 2.47889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39044E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4465 | ambiguous | 0.4838 | ambiguous | -2.548 | Highly Destabilizing | 0.116 | N | 0.703 | prob.neutral | None | None | None | None | N |
| I/C | 0.5615 | ambiguous | 0.5823 | pathogenic | -1.708 | Destabilizing | 0.944 | D | 0.675 | neutral | None | None | None | None | N |
| I/D | 0.8221 | likely_pathogenic | 0.8488 | pathogenic | -2.947 | Highly Destabilizing | 0.932 | D | 0.724 | prob.delet. | None | None | None | None | N |
| I/E | 0.7445 | likely_pathogenic | 0.7738 | pathogenic | -2.751 | Highly Destabilizing | 0.818 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/F | 0.1291 | likely_benign | 0.142 | benign | -1.517 | Destabilizing | 0.241 | N | 0.725 | prob.delet. | None | None | None | None | N |
| I/G | 0.7347 | likely_pathogenic | 0.7724 | pathogenic | -3.052 | Highly Destabilizing | 0.818 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/H | 0.4169 | ambiguous | 0.4493 | ambiguous | -2.485 | Highly Destabilizing | 0.893 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/K | 0.562 | ambiguous | 0.5896 | pathogenic | -2.099 | Highly Destabilizing | 0.773 | D | 0.731 | prob.delet. | N | 0.475808875 | None | None | N |
| I/L | 0.1148 | likely_benign | 0.1185 | benign | -1.101 | Destabilizing | 0.001 | N | 0.259 | neutral | N | 0.510571395 | None | None | N |
| I/M | 0.1105 | likely_benign | 0.1139 | benign | -0.952 | Destabilizing | 0.627 | D | 0.713 | prob.delet. | N | 0.493752227 | None | None | N |
| I/N | 0.3282 | likely_benign | 0.3618 | ambiguous | -2.345 | Highly Destabilizing | 0.818 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/P | 0.9746 | likely_pathogenic | 0.9773 | pathogenic | -1.564 | Destabilizing | 0.932 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/Q | 0.5152 | ambiguous | 0.5475 | ambiguous | -2.271 | Highly Destabilizing | 0.818 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/R | 0.4153 | ambiguous | 0.4442 | ambiguous | -1.674 | Destabilizing | 0.773 | D | 0.712 | prob.delet. | N | 0.50658694 | None | None | N |
| I/S | 0.3437 | ambiguous | 0.3751 | ambiguous | -2.978 | Highly Destabilizing | 0.388 | N | 0.703 | prob.neutral | None | None | None | None | N |
| I/T | 0.2775 | likely_benign | 0.3031 | benign | -2.656 | Highly Destabilizing | 0.324 | N | 0.716 | prob.delet. | N | 0.513187625 | None | None | N |
| I/V | 0.0674 | likely_benign | 0.0689 | benign | -1.564 | Destabilizing | None | N | 0.202 | neutral | N | 0.44088481 | None | None | N |
| I/W | 0.6843 | likely_pathogenic | 0.7067 | pathogenic | -1.933 | Destabilizing | 0.944 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/Y | 0.3735 | ambiguous | 0.394 | ambiguous | -1.659 | Destabilizing | 0.002 | N | 0.613 | 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.