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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000314.7(PTEN):c.1A>G (p.Met1Val)

CA377781751

484600 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b5f8e9e7-3f37-42d6-9844-c91a9757b411
Approved on: 2019-11-22
Published on: 2019-12-11

HGVS expressions

NM_000314.7:c.1A>G
NM_000314.7(PTEN):c.1A>G (p.Met1Val)
NC_000010.11:g.87864470A>G
CM000672.2:g.87864470A>G
NC_000010.10:g.89624227A>G
CM000672.1:g.89624227A>G
NC_000010.9:g.89614207A>G
NG_007466.2:g.6032A>G
NG_033079.1:g.3968T>C
NM_000314.5:c.1A>G
NM_000314.6:c.1A>G
NM_001304717.2:c.520A>G
NM_001304718.1:c.-705A>G
NM_001304717.5:c.520A>G
NM_001304718.2:c.-705A>G
ENST00000371953.7:c.1A>G
ENST00000462694.1:n.3A>G
ENST00000487939.1:n.22A>G
ENST00000610634.1:c.-102A>G

Pathogenic

Met criteria codes 4
PVS1 PS4_Moderate PM2 PM6
Not Met criteria codes 18
BA1 BS2 BS1 BS3 BS4 BP5 BP7 BP4 BP2 PS2 PS3 PS1 PP2 PP3 PP1 PM4 PM1 PM5

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.1A>G (p.M1?) 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5’ to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 29752200) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 29752200, 28774669; internal laboratory contributor ClinVar Organization ID: 26957)
Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4_Moderate
3 phenotype specificity points (see PP4 section).
PM2
Not present in gnomAD, coverage >90X.
PM6
Identified in a M Japanese patient (patient 6) as de novo, HC 60 @ 5yrs (+6 SD), sever DD, autism, distinctive facial features. Parents were healthy, but father had Graves' disease. They did not mention how the alteration was confirmed as de novo. CC score of 5 (Kato 2018 PubMed: 29752200)
PubMed:29752200
Not Met criteria codes
BA1
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
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
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
PS2
PubMed:29752200
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
PP2
Missense
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
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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