Variant: NM_002693.2(POLG):c.578G>A (p.Arg193Gln)

CA241475

21318 (ClinVar)

Gene: POLG

Condition: mitochondrial disease

Inheritance Mode: Autosomal recessive inheritance

UUID: 32aa42c6-6e27-46ba-a061-ce5f93499fbc

Approved on: 2021-05-07

Published on: 2021-05-23

HGVS expressions

NM_002693.2:c.578G>A
NM_002693.2(POLG):c.578G>A (p.Arg193Gln)
NC_000015.10:g.89333177C>T
CM000677.2:g.89333177C>T
NC_000015.9:g.89876408C>T
CM000677.1:g.89876408C>T
NC_000015.8:g.87677412C>T
NG_008218.1:g.6619G>A
NG_008218.2:g.6619G>A
ENST00000268124.11:c.578G>A
ENST00000530292.3:n.179G>A
ENST00000635986.2:c.578G>A
ENST00000636774.1:c.578G>A
ENST00000650303.2:n.633G>A
ENST00000666746.1:n.235G>A
ENST00000672071.1:n.776G>A
ENST00000268124.9:c.578G>A
ENST00000442287.6:c.578G>A
ENST00000631044.2:c.578G>A
NM_001126131.1:c.578G>A
NM_001126131.2:c.578G>A
NM_002693.3:c.578G>A

Uncertain Significance

• Met criteria codes: BS2

• Not Met criteria codes: BS1 BP4 BA1

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The c.578G>A (p.Arg193Gln) variant in POLG has been reported with an allele frequency in the population at 0.2 % in African Americans in gnomAD. It is also seen in the homozygous state in 1 individual in gnomAD (BS2). This variant is not reported in the literature and no computational data is available. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: BS2.

Met criteria codes

• BS2: 1 homozygote

Not Met criteria codes

• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: REVEL score 0.16
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline