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]

Variant: NM_000314.7(PTEN):c.947T>C (p.Leu316Pro)

CA16619068

418653 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 255886f5-38f4-41db-b167-02609497e697
Approved on: 2024-02-09
Published on: 2024-03-04

HGVS expressions

NM_000314.7:c.947T>C
NM_000314.7(PTEN):c.947T>C (p.Leu316Pro)
NC_000010.11:g.87961039T>C
CM000672.2:g.87961039T>C
NC_000010.10:g.89720796T>C
CM000672.1:g.89720796T>C
NC_000010.9:g.89710776T>C
NG_007466.2:g.102601T>C
ENST00000700029.2:c.1040T>C
ENST00000710265.1:c.947T>C
ENST00000472832.3:c.947T>C
ENST00000688158.2:n.1682T>C
ENST00000688922.2:c.*777T>C
ENST00000700021.1:c.902T>C
ENST00000700022.1:c.*286T>C
ENST00000700023.1:n.2105T>C
ENST00000700024.1:n.2339T>C
ENST00000700025.1:n.1716T>C
ENST00000700026.1:n.584T>C
ENST00000706954.1:c.947T>C
ENST00000706955.1:c.*982T>C
ENST00000686459.1:c.*533T>C
ENST00000688158.1:c.*1058T>C
ENST00000688308.1:c.947T>C
ENST00000688922.1:c.868T>C
ENST00000693560.1:c.1466T>C
ENST00000371953.8:c.947T>C
ENST00000371953.7:c.947T>C
ENST00000472832.2:c.374T>C
NM_000314.5:c.947T>C
NM_000314.6:c.947T>C
NM_001304717.2:c.1466T>C
NM_001304718.1:c.356T>C
NM_001304717.5:c.1466T>C
NM_001304718.2:c.356T>C
NM_000314.8:c.947T>C
NM_000314.8(PTEN):c.947T>C (p.Leu316Pro)
More

Likely Pathogenic

Met criteria codes 6
PM2_Supporting PS3_Moderate PP3 PP2 PM6 PS4_Supporting
Not Met criteria codes 20
BA1 BS4 BS3 BS1 BS2 PVS1 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS1 PP4 PP1 PM3 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
NM_000314.8(PTEN):c.947T>C (p.Leu316Pro) meets criteria to be classified as Likely Pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. ( internal laboratory contributor: SCV000565874.4) PS3_M: Functional studies showing a damaging effect on protein function. Phosphatase activity ≤ -1.11 per Mighell et al. 2018 (PMID: 29706350). This variant: score of -1.74442367. 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. PP3: REVEL score > 0.7 (score of this variant =0.77) PS4_P: Proband with phenotype specificity score of 2-3.5. (PMID:30311381, internal laboratory contributor: SCV000565874.4)
Met criteria codes
PM2_Supporting
absent gnomAD
PS3_Moderate
Mighell et al. 2018 PMID: 29706350: Lipid phosphatase activity score, -1.74442367 (TRUE).
PP3
in silico REVEL score of 0.77 (>0.7)
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. ( internal laboratory contributor: SCV000565874.4)
PS4_Supporting
Proband with phenotype specificity score of 2-3.5. (PMID:30311381, internal laboratory contributor: SCV000565874.4)
Not Met criteria codes
BA1
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
BS3
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
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
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
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
BP1
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
2 meioses.
PM3
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
PM4
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
Curation History
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