Table 1.
Annotation of 17 known pathogenic variants.
| ClinVar annotations | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Variant | Identifier | HGVS_transcript | HGVS_Predicted_Protein | Carrier | Sanger | MAF gnomAD | CADD | 2014–2018 | 2020 stars | Submissions |
| RET | chr10:43609097_G>A | rs79781594 | NM_020630.5:c.1853G>A | NP_065681.1(LRG_518p2):p.(Cys618Tyr) | A1 | + | . | 19 | 5,5,5,5,5 | 2/4 | 2 |
| PTEN | chr10:89685307_T>C | rs398123317 | NM_000314.5:c.202T>C | NP_000305.3(LRG_311p1):p.(Tyr68His) | B1 | + | . | 23 | 0,0,5,3,5 | 2/4 | 1 |
| KCNQ1 | chr11:2591882_G>A | rs179489 | NM_000218.2:c.502G>A | NP_000209.2(LRG_287p1):p.(Gly168Arg) | C1 | + | 0.000012 | 30 | 3,4,4,4,5 | 2/4 | 3 |
| KCNQ1 | chr11:2591949_G>A | rs120074178 | NM_000218.2:c.569G>A | NP_000209.2(LRG_287p1):p.(Arg190Gln) | D1 | + | 0.000004 | 35 | 4,4,5,4,5 | 2/4 | 4 |
| MYBPC3 | chr11:47356671_G>A | rs387907267 | NM_000256.3:c.2827C>T | NP_000247.2(LRG_386p1):p.(Arg943Ter) | E1 | + | 0.000012 | 39 | 5,5,5,5,5 | 2/4 | 9 |
| MYL2 | chr12:111348980_C>G | rs199474813 | NM_000432.3:c.403–1G>C | NP_000423.2(LRG_393p1):p.? | F1 | + | 2/4 | 2 | |||
| F2 | + | ||||||||||
| F3 | + | ||||||||||
| F4 | + | 0.000045 | 16 | 3,4,4,4,5 | |||||||
| F5 | + | ||||||||||
| F6 | + | ||||||||||
| F7 | + | ||||||||||
| MYL2 | chr12:111356937_C>T | rs104894368 | NM_000432.3:c.64G>A | NP_000423.2(LRG_393p1):p.(Glu22Lys) | G1 | + | 0.000020 | 33 | 5,3,4,4,5 | 2/4 | 9 |
| BRCA2 | chr13:32900281_AA>- | rs397507739 | NM_000059.3:c.469_470del | NP_000050.2(LRG_293p1):p.(Lys157ValfsTer25) | H1 | + | . | . | 4,4,4,4,5 | 3/4 | 6 |
| BRCA2 | chr13:32930747_G>T | rs397507922 | NM_000059.3:c.7617+1G>T | NP_000050.2(LRG_293p1):p.? | I1 | + | . | 21 | 0,5,3,5,5 | 2/4 | 4 |
| BRCA2 | chr13:32936831_G>A | rs81002873 | NM_000059.3:c.7976+1G>A | NP_000050.2(LRG_293p1):p.? | J1 | - | . | 29 | 4,4,4,4,5 | 3/4 | 4 |
| J2 | - | ||||||||||
| BRCA1 | chr17:41209068_C>T | rs80358150 | NM_007300.3:c.5340+1G>A | NP_009231.2:p.? | K1 | + | . | 18 | 0,3,5,4,5 | 3/4 | 13 |
| DSC2 | chr18:28667778_T>C | rs397514042 | NM_024422.3:c.631–2A>G | NP_077740.1:p.? | L1 | + | 0.000016 | 9 | 5,3,4,5,5 | 1/4 | 2 |
| DSG2 | chr18:29116261_G>A | rs121913009 | NM_001943.3:c.1520G>A | NP_001934.2(LRG_397p1):p.(Cys507Tyr) | M1 | + | . | 15 | 5,5,5,5,5 | 0/4 | 1 |
| LDLR | chr19:11210962_G>A | rs267607213 | NM_000527.4:c.131G>A | NP_000518.1(LRG_274p1):p.(Trp44Ter) | N1 | + | . | 25 | 5,5,3,3,5 | 2/4 | 13 |
| RYR1 | chr19:38948185_C>T | rs118192172 | NM_000540.2:c.1840C>T | NP_000531.2(LRG_766p1):p.(Arg614Cys) | O1 | + | 16 | 3,3,3,4,5 | 3/4 | 5 | |
| O2 | + | 0.000097 | |||||||||
| O3 | + | ||||||||||
| RYR1 | chr19:38986923_C>T | rs118192177 | NM_000540.2:c.6617C>T | NP_000531.2(LRG_766p1):p.(Thr2206Met) | P1 | + | 0.000012 | 17 | 0,3,4,3,5 | 2/4 | 2 |
| RYR1 | chr19:39071043_G>A | rs118192168 | NM_000540.2:c.14545G>A | NP_000531.2(LRG_766p1):p.(Val4849Ile) | Q1 | + | 0.000016 | 17 | 5,4,4,4,5 | 3/4 | 2 |
For each variant the genomic location (build hg37), single-nucleotide polymorphism (SNP) identifier, Human Genome Variation Society (HGVS) coding, minor allele frequency (MAF) in the gnomAD exome database, CADD score, and ClinVar classification class for the five tested version time points (2014–2018) are indicated. All variants had classification 5 according to the Human Gene Mutation Database (HGMD) and the 2018 version of ClinVar. In addition, the pathogenic classification of each variant was confirmed in the most recent online ClinVar database (09-04-2020, 9 April 2020). For each variant the 2020 ClinVar star rating and number of submission are shown. In ClinVar, the following definition is giving for these star classifications: 0: no assertion criteria provided; 1: criteria provided, conflicting interpretation; 2: criteria provided, multiple submitters; 3: reviewed by expert panel. The column “Sanger” denotes confirmed (+) (24 samples) or unconfirmed (-) (2 samples) by Sanger sequencing.