MUTATION NOMENCLATURE

Question 1

impact of nonsense mutation

Answer 1

1. No protein due to nonsense-mediated
   decay
2. Truncated protein

Question 2

impact of indel

Answer 2

1. In frame (usually milder)
2. Frameshift (usually more severe)
   • Often leads to a premature stop codon

Question 3

impact of splice site

Answer 3

1. Intron retention

2. Exon skipping

Question 4

Cryptic splice site

Answer 4

Splicing at the wrong position

Question 5

c.372G/A

Answer 5

coding DNA sequence where G is the 372 th coding nucleotide in a gene sequence replaced by A

Question 6

g.44921A/G

Answer 6

genomic sequence, A is the 44921 th nucleotide in the reference genomic sequence replaced by G

Question 7

PROTEIN nomenclature

Answer 7

1. Codon numbers are written on
   top of a sequence

2.* When you are asked to transcribe a 5’-3’ DNA
sequence into mRNA, simply rewrite the sequence,
but replace T with U!

• NEVER reverse and/or complement the sequence

Question 8

p.Ala23Pro

Answer 8

protein level, amino acid Ala in codon number 23 has changed to Pro

Question 9

silent mutation nomenclature

Answer 9

Only makes sense to describe at the coding/genomic level,

since there is no amino acid change in the protein

Question 10

missense mutation nomenclature

Answer 10

q Can be written at both coding and protein levels

e.g. c.382A>C p.Lys128Gln p.K128Q

Question 11

nonsense mutation nomenclature

Answer 11

A stop codon is denoted by the abbreviation “Ter” for
termination
e.g. c.382A>T p.Lys128Ter p.K128*

Question 12

Nucleotide substitutions in introns

Answer 12

1.Specify the coding nucleotide number first, then the
distance from the splice site
2. Nucleotides are still written with capital letters even when referring to intronic mutations! Lowercase only used for “r.” nomenclature

Question 13

c. 134+1G>T
c. 135-1G>T
c. 1-1C>A

Answer 13

1. coding nucleotide 134 is 1 base away from the mutated nucleotide where G is replaced by T
2. for negative, the introns nucleotide are on the left side therefore we use a negative

Question 14

INDEL nomenclature

Answer 14

Use del for deletions and ins for insertions.

The nucleotide position or amino acid symbol comes first

Question 15

e.g.
c.73_77delATAAG
c.13_15delACT (p.Thr5del or p.T5del) in frame del of
threonine

Answer 15

1. nucleotide 73 to 77 were deleted

2. Thr is codon number 5 was deleted

Question 16

c. 409_410insC

p. K29_M30insQSK

Answer 16

1. between nucleotide 409 and 410 there was an insertion of C
2. between aminoacid K in codon 29 and aminoacid M in codon 30 there was an insertion of QSK

Question 17

duplication nomenclature

Answer 17

Use “dup” to indicate a duplication event

Question 18

1. c.77_79dupCTG

2. p.G31_Q33dupGHQ

Answer 18

1. indicates that nucleotides 77 to 79
   (inclusive) were duplicated
2. indicates that amino acids 31 to 33
   were duplicated. For brevity, it is often simply written as
   p.G31_Q33dup

Question 19

Note that mutation nomenclature is always written

from the perspective of the NORMAL sequence

Answer 19

true