DNA Variant ID (HGVS) Using Sanger Sequencing

Question 1

HGVS Nomenclature

Answer 1

• uses letter prefixes to indicate type of reference sequence

c. = coding DNA
g. = genomic DNA
m. = mitochondrial DNA
p. = protein
r. = RNA

• assumes variant is in the 3- most position

ATGCAAAT vs ATGCAAT

Question 2

Where does coding DNA start in HGVS nomenclature ?

Answer 2

Start at ATG translational start site

A = 1

Question 3

Protein counting in HGVS nomenclature

Answer 3

Start counting at the first MET

Question 4

Abbrev. for substitution

Answer 4

>

Question 5

Abbrev. for insertion

Answer 5

“ins”

c.76_77insG = a G was inserted between nt 76 and 77

Question 6

Abbrev. for frame shift

Answer 6

fs

Question 7

Abbrev. for extension

Answer 7

ext

Question 8

T or F: with protein naming, NEVER look at the DNA change

Answer 8

TRUE: with protein naming, NEVER look at the DNA change. You only care what it does to the protein

Question 9

Use of round parentheses in HGVS nomenclature

Answer 9

Indicates uncertainty:

DNA = uncertainty of breakpoints
Protein = protein change is predicted based on DNA change (not experimental evidence)

Question 10

Use of square parantheses in HGVS

Answer 10

Allele location (same or opposite chromosomes)

Question 11

Which variants are detected by Sanger Sequencing ?

Answer 11

• synonymous
• missense
• nonsense
• insertions
• duplications
• deletions
• indels (insertion + deletions)