Table 1 Annotation of 17 known pathogenic variants.

From: Reduced penetrance of pathogenic ACMG variants in a deeply phenotyped cohort study and evaluation of ClinVar classification over time

         

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

  1. 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.
Back to article page