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]
  • See Evidence submitted by expert panel for details.

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: 2019-06-25
Published on: 2019-07-23

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
ENST00000700029.2:c.934C>G
ENST00000710265.1:c.841C>G
ENST00000472832.3:c.841C>G
ENST00000688158.2:n.1576C>G
ENST00000688922.2:c.*671C>G
ENST00000700021.1:c.796C>G
ENST00000700022.1:c.*180C>G
ENST00000700023.1:n.1999C>G
ENST00000700024.1:n.2233C>G
ENST00000700025.1:n.1610C>G
ENST00000700026.1:n.478C>G
ENST00000700029.1:c.768C>G
ENST00000706954.1:c.841C>G
ENST00000706955.1:c.*876C>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
More

Uncertain Significance

Met criteria codes 3
PM2 PP2 BS3_Supporting
Not Met criteria codes 23
PM1 PM3 PM5 PM4 PS1 PS2 PS3 PS4 BA1 PM6 PP1 PP3 PP4 PVS1 BS1 BS4 BS2 BP5 BP7 BP4 BP3 BP1 BP2

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
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. BS3_P: In vitro or in vivo functional study or studies showing no damaging effect on protein function but BS3 not met. (PMID 29706350)
Met criteria codes
PM2
absent gnomAD I agree (FH)
PP2
I agree (FH)
BS3_Supporting
Wouldn't apply full BS3 b/c only 2 replicates in Matreyek, and would also want EP to approve as "second assay" for this domain. FH: BS3_supporting wt-like in Matreyek (1.37)
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
Not Met criteria codes
PM1
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
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
PS1
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
PS3
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
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
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
PP4
See PS4
PVS1
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
BS4
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
BP4
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
BP1
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
Curation History
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