Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13956 | 42091;42092;42093 | chr2:178635458;178635457;178635456 | chr2:179500185;179500184;179500183 |
| N2AB | 12315 | 37168;37169;37170 | chr2:178635458;178635457;178635456 | chr2:179500185;179500184;179500183 |
| N2A | 11388 | 34387;34388;34389 | chr2:178635458;178635457;178635456 | chr2:179500185;179500184;179500183 |
| N2B | 4891 | 14896;14897;14898 | chr2:178635458;178635457;178635456 | chr2:179500185;179500184;179500183 |
| Novex-1 | 5016 | 15271;15272;15273 | chr2:178635458;178635457;178635456 | chr2:179500185;179500184;179500183 |
| Novex-2 | 5083 | 15472;15473;15474 | chr2:178635458;178635457;178635456 | chr2:179500185;179500184;179500183 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1176642239  |
-1.577 | 0.999 | D | 0.701 | 0.452 | 0.589992848803 | gnomAD-2.1.1 | 4.2E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.34E-06 | 0 |
| A/T | rs1176642239 |
-1.577 | 0.999 | D | 0.701 | 0.452 | 0.589992848803 | gnomAD-4.0.0 | 1.60727E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88264E-06 | 0 | 0 |
| A/V | rs2060324765 |
None | 0.999 | D | 0.663 | 0.47 | 0.61427494375 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8609 | likely_pathogenic | 0.8238 | pathogenic | -0.862 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| A/D | 0.9967 | likely_pathogenic | 0.9968 | pathogenic | -2.078 | Highly Destabilizing | 0.999 | D | 0.897 | deleterious | None | None | None | None | N |
| A/E | 0.9932 | likely_pathogenic | 0.9938 | pathogenic | -1.954 | Destabilizing | 1.0 | D | 0.85 | deleterious | D | 0.643214195 | None | None | N |
| A/F | 0.9896 | likely_pathogenic | 0.9887 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| A/G | 0.4741 | ambiguous | 0.3315 | benign | -1.404 | Destabilizing | 0.262 | N | 0.271 | neutral | D | 0.642739009 | None | None | N |
| A/H | 0.9961 | likely_pathogenic | 0.9959 | pathogenic | -1.877 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| A/I | 0.9827 | likely_pathogenic | 0.9813 | pathogenic | 0.062 | Stabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| A/K | 0.998 | likely_pathogenic | 0.9975 | pathogenic | -1.319 | Destabilizing | 0.999 | D | 0.868 | deleterious | None | None | None | None | N |
| A/L | 0.9413 | likely_pathogenic | 0.9386 | pathogenic | 0.062 | Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| A/M | 0.9708 | likely_pathogenic | 0.969 | pathogenic | 0.032 | Stabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| A/N | 0.9915 | likely_pathogenic | 0.9914 | pathogenic | -1.357 | Destabilizing | 0.999 | D | 0.891 | deleterious | None | None | None | None | N |
| A/P | 0.9965 | likely_pathogenic | 0.9953 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.645071945 | None | None | N |
| A/Q | 0.9849 | likely_pathogenic | 0.9834 | pathogenic | -1.291 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| A/R | 0.9902 | likely_pathogenic | 0.9883 | pathogenic | -1.23 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| A/S | 0.3909 | ambiguous | 0.3709 | ambiguous | -1.717 | Destabilizing | 0.991 | D | 0.491 | neutral | D | 0.641211923 | None | None | N |
| A/T | 0.7898 | likely_pathogenic | 0.7815 | pathogenic | -1.488 | Destabilizing | 0.999 | D | 0.701 | prob.delet. | D | 0.641963446 | None | None | N |
| A/V | 0.8653 | likely_pathogenic | 0.855 | pathogenic | -0.246 | Destabilizing | 0.999 | D | 0.663 | prob.neutral | D | 0.641963446 | None | None | N |
| A/W | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/Y | 0.9961 | likely_pathogenic | 0.996 | pathogenic | -0.931 | Destabilizing | 1.0 | D | 0.905 | 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.