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.1093G>A (p.Val365Ile)

CA059160

237639 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1ebd3f87-9825-4ccc-aa05-14d1b0b78d24
Approved on: 2023-12-01
Published on: 2023-12-14

HGVS expressions

NM_000314.7:c.1093G>A
NM_000314.7(PTEN):c.1093G>A (p.Val365Ile)
NC_000010.11:g.87965353G>A
CM000672.2:g.87965353G>A
NC_000010.10:g.89725110G>A
CM000672.1:g.89725110G>A
NC_000010.9:g.89715090G>A
NG_007466.2:g.106915G>A
ENST00000686459.1:c.*679G>A
ENST00000688158.1:c.*1204G>A
ENST00000688308.1:c.1093G>A
ENST00000688922.1:c.1014G>A
ENST00000693560.1:c.1612G>A
ENST00000371953.8:c.1093G>A
ENST00000371953.7:c.1093G>A
NM_000314.5:c.1093G>A
NM_000314.6:c.1093G>A
NM_001304717.2:c.1612G>A
NM_001304718.1:c.502G>A
NM_001304717.5:c.1612G>A
NM_001304718.2:c.502G>A
NM_000314.8:c.1093G>A
NM_000314.8(PTEN):c.1093G>A (p.Val365Ile)
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Uncertain Significance

Met criteria codes 3
PM2_Supporting BP4 PP2
Not Met criteria codes 23
BA1 BS4 BS3 BS1 BS2 PVS1 BP5 BP7 BP2 BP1 BP3 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PM6 PM3 PM1 PM5 PM4

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
PTEN c.1093G>A (p.Val365Ile) is currently classified as a variant of uncertain significance 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). PM2: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (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. BP4: REVEL score < 0.5 (score=0.441) Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign supporting and 2 pathogenic supporting codes get -1 + (1*2) points; total is 1 (VUS).
Met criteria codes
PM2_Supporting
Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. AF=0.000004973 in gnomAD 4.0
BP4
REVEL score < 0.5 (score=0.441)
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.
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
Matreyek results is WT-like (1.140914254). Mighell results is WT-like (-0.102592235) but not >0 so BS3 does not apply.
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
GeneDx internal data: 1 patient with breast and CRC dx 40s and father brain dx 50s. Harbors ATM variant.
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
BP1
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
GeneDx internal data: 2 patients with CC score = 1.
PS3
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
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
Curation History
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