Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22829 | 68710;68711;68712 | chr2:178578030;178578029;178578028 | chr2:179442757;179442756;179442755 |
| N2AB | 21188 | 63787;63788;63789 | chr2:178578030;178578029;178578028 | chr2:179442757;179442756;179442755 |
| N2A | 20261 | 61006;61007;61008 | chr2:178578030;178578029;178578028 | chr2:179442757;179442756;179442755 |
| N2B | 13764 | 41515;41516;41517 | chr2:178578030;178578029;178578028 | chr2:179442757;179442756;179442755 |
| Novex-1 | 13889 | 41890;41891;41892 | chr2:178578030;178578029;178578028 | chr2:179442757;179442756;179442755 |
| Novex-2 | 13956 | 42091;42092;42093 | chr2:178578030;178578029;178578028 | chr2:179442757;179442756;179442755 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/Q | rs747495409  |
-1.027 | 1.0 | N | 0.777 | 0.452 | 0.427254322456 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/Q | rs747495409 |
-1.027 | 1.0 | N | 0.777 | 0.452 | 0.427254322456 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/Q | rs747495409 |
-1.027 | 1.0 | N | 0.777 | 0.452 | 0.427254322456 | gnomAD-4.0.0 | 1.97272E-05 | None | None | None | None | I | None | 7.24113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1065 | likely_benign | 0.1015 | benign | -1.348 | Destabilizing | 0.767 | D | 0.356 | neutral | N | 0.474669309 | None | None | I |
| P/C | 0.6039 | likely_pathogenic | 0.6035 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| P/D | 0.9468 | likely_pathogenic | 0.9575 | pathogenic | -1.28 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| P/E | 0.8431 | likely_pathogenic | 0.8655 | pathogenic | -1.357 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| P/F | 0.7279 | likely_pathogenic | 0.7469 | pathogenic | -1.297 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| P/G | 0.6314 | likely_pathogenic | 0.6445 | pathogenic | -1.577 | Destabilizing | 0.997 | D | 0.62 | neutral | None | None | None | None | I |
| P/H | 0.6182 | likely_pathogenic | 0.6615 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| P/I | 0.6151 | likely_pathogenic | 0.6223 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| P/K | 0.899 | likely_pathogenic | 0.9178 | pathogenic | -1.058 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| P/L | 0.3855 | ambiguous | 0.399 | ambiguous | -0.846 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | N | 0.502066658 | None | None | I |
| P/M | 0.5773 | likely_pathogenic | 0.5903 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/N | 0.8236 | likely_pathogenic | 0.8384 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| P/Q | 0.6053 | likely_pathogenic | 0.6169 | pathogenic | -1.006 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.504094574 | None | None | I |
| P/R | 0.7829 | likely_pathogenic | 0.8193 | pathogenic | -0.408 | Destabilizing | 0.999 | D | 0.751 | deleterious | N | 0.488610439 | None | None | I |
| P/S | 0.3514 | ambiguous | 0.3534 | ambiguous | -1.107 | Destabilizing | 0.992 | D | 0.609 | neutral | N | 0.475924234 | None | None | I |
| P/T | 0.3465 | ambiguous | 0.375 | ambiguous | -1.095 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | N | 0.497257719 | None | None | I |
| P/V | 0.3965 | ambiguous | 0.4011 | ambiguous | -0.979 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | I |
| P/W | 0.8921 | likely_pathogenic | 0.9012 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| P/Y | 0.7368 | likely_pathogenic | 0.7709 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
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.