The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_002693.2(POLG):c.3572A>G (p.Lys1191Arg)

CA10602281

619340 (ClinVar)

Gene: POLG
Condition: mitochondrial disease
UUID: ec04cb74-5c03-44ee-974b-e754627cb46f
Approved on: 2021-05-06
Published on: 2021-05-06

HGVS expressions

NM_002693.2:c.3572A>G
NM_002693.2(POLG):c.3572A>G (p.Lys1191Arg)
ENST00000268124.11:c.3572A>G
ENST00000530292.3:n.3272A>G
ENST00000635986.2:c.*642A>G
ENST00000636774.1:c.*2176A>G
ENST00000637042.1:n.96A>G
ENST00000637238.1:n.2480A>G
ENST00000637264.1:n.2584A>G
ENST00000666746.1:n.3149A>G
ENST00000672071.1:n.4774A>G
ENST00000672695.1:n.1351A>G
ENST00000672923.2:n.3572A>G
ENST00000268124.9:c.3572A>G
ENST00000442287.6:c.3572A>G
ENST00000526671.1:n.382A>G
ENST00000530292.2:n.755A>G
ENST00000631044.2:c.*2996A>G
NM_001126131.1:c.3572A>G
NM_001126131.2:c.3572A>G
NM_002693.3:c.3572A>G
NC_000015.10:g.89317447T>C
CM000677.2:g.89317447T>C
NC_000015.9:g.89860678T>C
CM000677.1:g.89860678T>C
NC_000015.8:g.87661682T>C
NG_008218.1:g.22349A>G
NG_011736.1:g.78485T>C
NG_008218.2:g.22349A>G
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Uncertain Significance

Met criteria codes 4
PM2 PM5_Supporting PM3_Supporting PP3
Not Met criteria codes 1
PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The c.3572 A>G (p.Lys1191Arg) variant in POLG is absent in population databases (PM2). Computational prediction tool Revel score 0.938 (PP3). This variant has been reported in trans with c.752 C>T (p.Thr251Ile) / c.1760 C>T (p.Pro587Leu) in a 1 year old who presented with Childhood myocerebrohepatopathy spectrum and pancreatisis (PM3_supporting; PMID: 18546365). There is a likely pathogenic variant at the same amino acid position p.Lys1191Asn seen in 3 cases as compound heterozygotes. Two cases with Ala467Thr presenting with Alpers syndrome and one with c.752 C>T (p.Thr251Ile) / c.1760 C>T (p.Pro587Leu) presenting with CPEO spectrum (PM5_supporting; PMID: 16621917; PMID: 21880868; PMID: 19538466). In summary, there is insufficient evidence to characterize this variant and therefore it remains a variant of uncertain significance for primary mitochondrial disease inherited in a autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: PM2, PM3_strong, PP3, PM5_supporting.
Met criteria codes
PM2
Absent from databases
PM5_Supporting
K1191N likely path
PM3_Supporting
Seen in trans confirmed with T251I+p.P587L
PP3
Revel score > 0.75 Revel score 0.938
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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