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.841C>G (p.Pro281Ala)

CA000211

184466 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 74ec7748-2294-4f8c-a299-53b2a9c51d35
Approved on: 2023-10-11
Published on: 2023-10-18

HGVS expressions

NM_000314.6:c.841C>G
NM_000314.6(PTEN):c.841C>G (p.Pro281Ala)
NC_000010.11:g.87960933C>G
CM000672.2:g.87960933C>G
NC_000010.10:g.89720690C>G
CM000672.1:g.89720690C>G
NC_000010.9:g.89710670C>G
NG_007466.2:g.102495C>G
ENST00000686459.1:c.*427C>G
ENST00000688158.1:c.*952C>G
ENST00000688308.1:c.841C>G
ENST00000688922.1:c.762C>G
ENST00000693560.1:c.1360C>G
ENST00000371953.8:c.841C>G
ENST00000371953.7:c.841C>G
ENST00000472832.2:c.268C>G
NM_000314.5:c.841C>G
NM_001304717.2:c.1360C>G
NM_001304718.1:c.250C>G
NM_000314.7:c.841C>G
NM_001304717.5:c.1360C>G
NM_001304718.2:c.250C>G
NM_000314.8:c.841C>G
NM_000314.8(PTEN):c.841C>G (p.Pro281Ala)
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Uncertain Significance

Met criteria codes 2
PP2 PM2_Supporting
Not Met criteria codes 24
PS2 PS4 PS3 PS1 PP4 PP1 PP3 PVS1 PM3 PM1 PM4 PM5 BA1 PM6 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1

Evidence Links 3

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.841C>G (p.Pro281Ala) 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.
Met criteria codes
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.
PM2_Supporting
Absent in gnomAD
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
1 internal case from Charis Eng's lab: female age 49, consented age 47 CC Score: 1; OFC: 53.25 cm; Normal Head Size; Thyroid Nodule; Fibrocystic Breast Disease; Uterine Fibroids; Family: none; Other genotypes: none. Does not meet criteria for PS4, PS4_moderate, or PS4_supporting.
Variant identified in a pt with pancreatic cancer; no other info provided. PubMed:29945567
PS3
Variant showed WT-like protein stability (score = 1.37) but only 2 experimental replicates. PubMed:29785012
Phosphatase activity at low end of WT-like range (-1.03, hypomorphic starts at -1.11). PubMed:29706350
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
See PS4
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
PVS1
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
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
BA1
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Mighell et al. 2018 PMID: 29706350: Lipid phosphatase activity score, -1.03673832 (FALSE) Matreyek et al. 2018 PMID: 29785012: abundance_class is WT-like.
Variant showed WT-like protein stability (score = 1.37) but only 2 experimental replicates. PubMed:29785012
Phosphatase activity at low end of WT-like range (-1.03, hypomorphic starts at -1.11). PubMed:29706350
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
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
Curation History
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