POLG Pathogenicity Prediction Server

POLG Pathogenicity Prediction Server

Mutation Query

Allele 1:

Y831C

Allele 2:

R722H

Allelic information known

Amino Acid Residue Information

722831

Residue R722

Cluster assignment:

SNP

Cluster description:

Single Nucleotide Polymorphism

POLG domain:

Spacer domain

Residue Y831

Cluster assignment:

SNP

Cluster description:

Single Nucleotide Polymorphism

POLG domain:

Polymerase domain

Mutation Information

Number of patients:

(with Y831C)

7

Found as the only mutation:

57% of entries (4 patients)

Found together with:

Non-allelic

%

Allelic

%

Show Patient Data

Patient data are sorted by mutation combination frequency.

Reference:

Mancuso et al, 2004b;

1

Description:

Presented with progressive bilateral ptosis, diplopia, muscle weakness, and exercise intolerance at 28 years of age. Ophthalmoplegia and severe bilateral ptosis developed by age 44, sensory neuropathy at age 45, and at age 47 she developed slowly progressive resting hand tremor, slowing of her gait, bradykinesia, rigidity, and slurred speech. Muscle biopsy showed numerous ragged-red fibers and Southern blot analysis showed multiple deletions of mtDNA. insipient parkinsonism.

Mutations:

SNPs:

Y831C

Age group:

adult

Age of Onset: 28, Age of Patient: 49, Age of Death: n/a

Reference:

Woodbridge et al, 2012;

2

Description:

CPEO, Seizures, neuropathy, ataxia, hepatopathy, dysphagia/ dysarthria, gastric and small bowel dysmotility after a colectomy, and multiple admissions for recurrent pseudo-obstruction, proximal myopathy,

Mutations:

SNPs:

Y831C

Age group:

juvenile

Age of Onset: n/a, Age of Patient: 34, Age of Death: n/a

Reference:

Woodbridge et al, 2012;

3

Description:

Seizures, liver function tests change, migraine, increasing proximal weakness and myalgia, mild asymmetrical ptosis

Mutations:

SNPs:

Y831C

Age group:

adult

Age of Onset: n/a, Age of Patient: 46, Age of Death: n/a

Reference:

Barthelemy et al, 2002;

4

Description:

severe mitochondrial DNA depletion in muscle and kidney. Patient also has heteroplasmic mtDNA alterations including large-size deletions and point mutations in the D-loop region. Severe sensorineural deafness, intolerance to exercise and nephrotic syndrome. Retinitis pigmentosa, optic atrophy, ophthalmoplegia, epilepsy, mental deterioration and permanent muscle weakness with diffuse myalgia and respiratory distress.

Mutations:

SNPs:

Y831C

Age group:

childhood

Age of Onset: 6, Age of Patient: n/a, Age of Death: 13

Reference:

Taanman et al, 2009;

5

Description:

Anorexia, FTT, drowsiness, hepatomegaly, peripheral odema, liver failure. Onset at 3 months with infantile hepatocerebral mtDNA depletion. Death at 6 months. Asymptomatic mother and father.

Mutations:

SNPs:

Y831C

Age group:

infantile

Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.5

Reference:

YlÃ¶nen et al, 2013;

6

Description:

late onset parkinsons. Tremor. Hyperreflexia.

Mutations:

SNPs:

R722H, Y831C

Age group:

adult

Age of Onset: 56, Age of Patient: n/a, Age of Death: n/a

Reference:

Luoma et al, 2007;

7

Description:

Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia. Ischemic Heart Disease, atrial fibrillation, hypertension

Mutations:

SNPs:

Q1236H, Y831C

Age group:

adult

Age of Onset: 70, Age of Patient: 79, Age of Death: n/a

Number of patients:

(with R722H)

17

Found as the only mutation:

59% of entries (10 patients)

Found together with:

Non-allelic

6

6

6

6

%

Allelic

6

%

Show Patient Data

Patient data are sorted by mutation combination frequency.

Reference:

Luoma et al, 2007;

1

Description:

Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia. Hypertension

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: 57, Age of Patient: 67, Age of Death: n/a

Reference:

Komulainen et al, 2010;

2

Description:

Cataract, balance disturbances, retinal rupture, tinnitus, unilateral deafness

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

3

Description:

Coronary heart disease, delayed puberty, sensorineural hearing loss

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

4

Description:

Delayed puberty, hypogonadism, transient vertigo, visual field defect

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

5

Description:

Diabetes mellitus, hypothyreosis, cerebral infarction, hypertension, hypercholesterolemia, learning difficulties

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

6

Description:

Hypothyreosis, gestational diabetes mellitus

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

7

Description:

Mental retardation

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

8

Description:

Premature puberty, short stature, fertility problems, gestational diabetes mellitus

Mutations:

SNPs:

R722H

Age group:

juvenile

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

9

Description:

Tinnitus, benign cardiac arrhythmias

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

10

Description:

Transient hypertension, benign cardiac arrhythmias, fertility problems

Mutations:

SNPs:

R722H

Age group:

adult

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Komulainen et al, 2010;

11

Description:

Mild dementia, sensorineural hearing impairment, diabetes mellitus, osteoarthritis, hypertension, coronary heart disease, areflexia due to diabetic neuropathy. She had a mild left motor hemiparesis at the age of 74 years due to a lacunar brain infarct. Patient A3. Elder sister of patient A1.

Mutations:

SNPs:

R722H, R722H

Age group:

adult

Age of Onset: 74, Age of Patient: 86, Age of Death: n/a

Reference:

Komulainen et al, 2010;

12

Description:

Moderate dementia, sensorineural hearing impairment, occasional headaches, bilateral cataract, chronic gastritis. Occasional headaches started at 30 years old. Patient A2. Younger sister of patient A1.

Mutations:

SNPs:

R722H, R722H

Age group:

adult

Age of Onset: 30, Age of Patient: 78, Age of Death: n/a

Reference:

Komulainen et al, 2010;

13

Description:

Severe dementia, sensorineural hearing impairment, diabetes mellitus, PEO, dysphagia, neuropathic pain in the legs, multiple mtDNA deletions in muscle. Clear age of onset not reported, hearing aid at 72 years. Patient A1.

Mutations:

SNPs:

R722H, R722H

Age group:

adult

Age of Onset: 72, Age of Patient: 83, Age of Death: n/a

Reference:

Komulainen et al, 2010;

14

Description:

mental retardation, psychiatric symptoms, mild bilateral ptosis and epilepsy, Seizures occurred at age 11 years, and focal generalized epilepsy was diagnosed.

Mutations:

SNPs:

E1143G, R722H

Age group:

childhood

Age of Onset: 11, Age of Patient: 22, Age of Death: n/a

Reference:

Bolszak et al, 2009;

15

Description:

Onset at 4 months with generalized tonic-clonic seizure, evolved to status epilepticus, treated with valproate, Progressive encephalopathy, and psychomotor development deficient by age 2, mentally retarded, ataxic and hyperkinetic. At the last follow-up visit at age 17 years, he was severely retarded, autistic, and ataxic. During 12 months of valproate treatment serum alanine aminotransferase (ALAT) increased from 29 to 71 U/L (normal < 40 U/L), and after discontinuation of the medication, ALAT values varied between 5 and 12 U/L.

Mutations:

SNPs:

R722H

Age group:

infantile

Age of Onset: 0.33, Age of Patient: 17, Age of Death: n/a

Reference:

YlÃ¶nen et al, 2013;

16

Description:

late onset parkinsons. Tremor. Hyperreflexia.

Mutations:

SNPs:

R722H, Y831C

Age group:

adult

Age of Onset: 56, Age of Patient: n/a, Age of Death: n/a

Reference:

Luoma et al, 2007;

17

Description:

Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia.

Mutations:

SNPs:

Q1236H, R722H

Age group:

adult

Age of Onset: 66, Age of Patient: 77, Age of Death: n/a

Pathogenicity Information

Database patient data suggest that Y831C is a known SNP.This mutation is unlikely to cause a POLG-related syndrome.

See full list of known POLG SNPs.

Database patient data suggest that R722H is a known SNP.This mutation is unlikely to cause a POLG-related syndrome.

See full list of known POLG SNPs.

Both genes contain only non-pathogenic SNPs according to the cluster analysis, and probability of pathogenicity can be considered to be low.

The following information is based on PON-P2 mutation pathogenicity prediction software results.

The PON-P2 sequence analysis prediction results below may or may not support this conclusion, but they should not be trusted on their own. All currently known pathogenic POLG-mutations are found within the assigned pathogenic clusters.

Gene1:

PON-P2 predictions results for Y831C
Pathogenicity:	Unreliable
Probability:	0.685
Standard Error:	0.225
Prediction result is based on sequence analysis only and may not be accurate.

Gene2:

PON-P2 predictions results for R722H
Pathogenicity:	Neutral
Probability:	0.057
Standard Error:	0.022
Prediction result is based on sequence analysis only and may not be accurate.

New Mutation Query

Type in POLG mutations:

Allele 1:	Allele 2:

Allelic information known
Allelic information not known

Example input: A467T T914P

Mutations in the same allele can be separated with a comma

:.: Privacy Statement :.: Disclaimer :.: Contact Information :.: