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_000314.7(PTEN):c.389G>C (p.Arg130Pro)

CA000439

142018 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 10bca2c6-405c-4f3a-919f-53db4e026879
Approved on: 2019-11-22
Published on: 2019-12-11

HGVS expressions

NM_000314.7:c.389G>C
NM_000314.7(PTEN):c.389G>C (p.Arg130Pro)
NC_000010.11:g.87933148G>C
CM000672.2:g.87933148G>C
NC_000010.10:g.89692905G>C
CM000672.1:g.89692905G>C
NC_000010.9:g.89682885G>C
NG_007466.2:g.74710G>C
NM_000314.5:c.389G>C
NM_000314.6:c.389G>C
NM_001304717.2:c.908G>C
NM_001304718.1:c.-362G>C
NM_001304717.5:c.908G>C
NM_001304718.2:c.-362G>C
ENST00000371953.7:c.389G>C
ENST00000498703.1:n.215G>C
ENST00000610634.1:c.287G>C
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Pathogenic

Met criteria codes 5
PS3 PP2 PM2 PM1 PS4_Supporting
Not Met criteria codes 15
BA1 BS1 BS3 BS4 BS2 BP5 BP7 BP4 BP2 PS1 PS2 PP3 PP1 PM6 PM4

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.389G>C (p.Arg130Pro) 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). PS3: Phosphatase activity <50% of wild type (PMID 29706350) PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. 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. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor SCV000185699.6)
Met criteria codes
PS3
High-throughput functional assay testing PTEN Lipid Phosphatase Activity. R130P had a score of -3.153431338 and was 'true' indicating function was truncation-like for PS3.
High-throughput functional assay testing PTEN Lipid Phosphatase Activity. R130P had a score of -3.153431338 and was 'true' indicating function was truncation-like for PS3. PubMed:29706350
PP2
Missense.
PM2
Not present in gnomAD (coverage >90X).
PM1
Affects amino acid position 130, which is in a catalytic motif.
PS4_Supporting
Proband in 60s with goiter, thyroid ca in 20s, kidney cancer in 60s, ganglioneuroma, >10 colon polyps, macrocephaly. (1 point) (Ambry Genetics).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
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
BP7
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
PM6
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
Curation History
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