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_000314.6(PTEN):c.104T>G (p.Met35Arg)

CA000268

7825 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 2374c339-e2d7-4496-9d9a-d33c1abd8dce
Approved on: 2018-07-25
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.104T>G
NM_000314.6(PTEN):c.104T>G (p.Met35Arg)
NC_000010.11:g.87894049T>G
CM000672.2:g.87894049T>G
NC_000010.10:g.89653806T>G
CM000672.1:g.89653806T>G
NC_000010.9:g.89643786T>G
NG_007466.2:g.35611T>G
NM_000314.5:c.104T>G
NM_001304717.2:c.623T>G
NM_001304718.1:c.-602T>G
NM_000314.7:c.104T>G
NM_001304717.5:c.623T>G
NM_001304718.2:c.-602T>G
ENST00000371953.7:c.104T>G
ENST00000462694.1:n.106T>G
ENST00000610634.1:c.2T>G
More

Pathogenic

Met criteria codes 4
PP2 PM2 PS3 PS2
Not Met criteria codes 18
PP3 PP1 PM5 PM4 PM1 PM6 BA1 BS2 PVS1 BS1 BS3 BS4 BP4 BP2 BP7 BP5 PS1 PS4

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.104T>G (p.Met35Arg) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (PMID 9425889) PS3: Phosphatase activity <50% of wild type. (PMID 21828076, 25875300) PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Met criteria codes
PP2
I Agree (FH)
PM2
variant not in gnomAD or other databases (MP) Per Felicia, I agree
PS3
I agree (FH)

PS2
Per Olschwang S et al, the genotypes at 8 highly polymorphic microsatellite loci in the parents and patient confirmed mendelian inheritance. Sequencing of exon 2 amplified from the DNAs of both parents revealed only codon 35 for methionine, demonstrating that codon 35 of arginine was a de novo mutation (FH). Per Expert Panel review, PS2 applies as opposed to PM6 (JM).

Not Met criteria codes
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
Parents of patient G710 were negative for variant. I disagree with PM6 (FH)

BA1
variant not in gnomAD or other databases (MP) Per Felicia, I agree
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
variant not in gnomAD or other databases (MP) Per Felicia, I agree
BS3
I agree (FH)
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.