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_000314.6(PTEN):c.364A>G (p.Ile122Val)

CA000147

186161 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c4bf5c74-cf88-47c3-812d-89a0c0e7f110
Approved on: 2021-06-04
Published on: 2022-09-30

HGVS expressions

NM_000314.6:c.364A>G
NM_000314.6(PTEN):c.364A>G (p.Ile122Val)
NC_000010.11:g.87933123A>G
CM000672.2:g.87933123A>G
NC_000010.10:g.89692880A>G
CM000672.1:g.89692880A>G
NC_000010.9:g.89682860A>G
NG_007466.2:g.74685A>G
ENST00000686459.1:c.364A>G
ENST00000688158.1:c.*475A>G
ENST00000688308.1:c.364A>G
ENST00000688922.1:n.285A>G
ENST00000693560.1:c.883A>G
ENST00000371953.8:c.364A>G
ENST00000371953.7:c.364A>G
ENST00000498703.1:n.190A>G
ENST00000610634.1:c.262A>G
NM_000314.5:c.364A>G
NM_001304717.2:c.883A>G
NM_001304718.1:c.-387A>G
NM_000314.7:c.364A>G
NM_001304717.5:c.883A>G
NM_001304718.2:c.-387A>G
NM_000314.8:c.364A>G
NM_000314.8(PTEN):c.364A>G (p.Ile122Val)
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Uncertain Significance

Met criteria codes 3
BS3 PP2 PM2
Not Met criteria codes 23
PVS1 BA1 BS2 BS1 BS4 BP2 BP1 BP4 BP3 BP5 BP7 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PM3 PM1 PM5 PM4 PM6

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.364A>G (p.Ile122Val) is currently classified as a variant of uncertain significance 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). 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. BS3: Missense variants with both lipid phosphatase activity AND results from a second assay appropriate to the protein domain demonstrating no statistically significant difference from wild type. (PMID 21828076, 29706350, 29785012)
Met criteria codes
BS3
PMID 21828076: demonstrated that missense change does not affect PTEN PIP3 phosphatase activity. I agree (FH)
Demonstrated that missense change does not affect PTEN PIP3 phosphatase activity. PubMed:21828076
Variant demonstrated WT-like abundance on high-throughput VAMPseq assay. PubMed:29785012
Variant demonstrated lipid phosphatase activity in WT-like range (score -0.48) on high throughput phosphatase assay. PubMed:29706350
PP2
PP2 applied because low rate of benign missense variation. I agree (FH)
PM2
Variant absent in population databases. I agree (FH)
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Variant absent in population databases. I agree (FH)
BS2
No healthy individual reported in the literature.
BS1
Variant absent in population databases. I agree (FH)
BS4
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
PP2 applied because low rate of benign missense variation. I agree (FH)
BP4
Cannot be applied as variant is a missense variant.
BP3
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
PS2
1 individual reported in ClinVar by Ambry with limited additional information.
PS4
No reported patients in the literature and no case/control studies found.
PS3
PMID 21828076: demonstrated that missense change does not affect PTEN PIP3 phosphatase activity. I agree (FH)
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
Cannot be applied as variant is a missense variant.
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Variant does not occur within specified residues.
PM5
Not applied because variant is not at likely pathogenic.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
1 individual reported in ClinVar by Ambry with limited additional information.
Curation History
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