Evidence Repository
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.3573G>T (p.Lys1191Asn)

CA10602282

426681 (ClinVar)

Gene: POLG
Condition: mitochondrial disease
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a57c4294-b4fc-47f9-a409-2182e7ab5ba1
Approved on: 2021-05-06
Published on: 2021-05-06

HGVS expressions

NM_002693.2:c.3573G>T
NM_002693.2(POLG):c.3573G>T (p.Lys1191Asn)
ENST00000268124.11:c.3573G>T
ENST00000530292.3:n.3273G>T
ENST00000635986.2:c.*643G>T
ENST00000636774.1:c.*2177G>T
ENST00000637042.1:n.97G>T
ENST00000637238.1:n.2481G>T
ENST00000637264.1:n.2585G>T
ENST00000666746.1:n.3150G>T
ENST00000672071.1:n.4775G>T
ENST00000672695.1:n.1352G>T
ENST00000672923.2:n.3573G>T
ENST00000268124.9:c.3573G>T
ENST00000442287.6:c.3573G>T
ENST00000526671.1:n.383G>T
ENST00000530292.2:n.756G>T
ENST00000631044.2:c.*2997G>T
NM_001126131.1:c.3573G>T
NM_001126131.2:c.3573G>T
NM_002693.3:c.3573G>T
NC_000015.10:g.89317446C>A
CM000677.2:g.89317446C>A
NC_000015.9:g.89860677C>A
CM000677.1:g.89860677C>A
NC_000015.8:g.87661681C>A
NG_008218.1:g.22350G>T
NG_011736.1:g.78484C>A
NG_008218.2:g.22350G>T
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Likely Pathogenic

Met criteria codes 3
PP3 PM2 PM3_Strong
Not Met criteria codes 1
BS2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The c.3573 G>T (K1191N) variant in POLG is absent in population databases (PM2 met). Computational prediction tool Revel score 0.876 (PP3 met Revel score > 0.75). This variant has been 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 (PM3_strong met; PMID: 16621917; PMID: 21880868; PMID: 19538466). In summary, this variant is characterized as a likely pathogenic variant for primary mitochondrial disease inherited in a autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: PM2, PM3_strong, PP3.
Met criteria codes
PP3
Revel score > 0.75 Revel score for variant 0.876
PM2
Absent from databases
PM3_Strong
3 cases all seen in as compound heterozygotes 2 with A467T and 1 with c.752 C>T (T251I) / c.1760 C>T (P587L). 2 cases had Alpers and 1 case had CPEO spectrum disorder.
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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