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.892C>G (p.Gln298Glu)

CA000623

127695 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 304beaf9-04a8-47e9-859a-ceb4b54a57fa
Approved on: 2019-03-05
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.892C>G
NM_000314.6(PTEN):c.892C>G (p.Gln298Glu)
NC_000010.11:g.87960984C>G
CM000672.2:g.87960984C>G
NC_000010.10:g.89720741C>G
CM000672.1:g.89720741C>G
NC_000010.9:g.89710721C>G
NG_007466.2:g.102546C>G
ENST00000700029.2:c.985C>G
ENST00000710265.1:c.892C>G
ENST00000472832.3:c.892C>G
ENST00000688158.2:n.1627C>G
ENST00000688922.2:c.*722C>G
ENST00000700021.1:c.847C>G
ENST00000700022.1:c.*231C>G
ENST00000700023.1:n.2050C>G
ENST00000700024.1:n.2284C>G
ENST00000700025.1:n.1661C>G
ENST00000700026.1:n.529C>G
ENST00000706954.1:c.892C>G
ENST00000706955.1:c.*927C>G
ENST00000686459.1:c.*478C>G
ENST00000688158.1:c.*1003C>G
ENST00000688308.1:c.892C>G
ENST00000688922.1:c.813C>G
ENST00000693560.1:c.1411C>G
ENST00000371953.8:c.892C>G
ENST00000371953.7:c.892C>G
ENST00000472832.2:c.319C>G
NM_000314.5:c.892C>G
NM_001304717.2:c.1411C>G
NM_001304718.1:c.301C>G
NM_000314.7:c.892C>G
NM_001304717.5:c.1411C>G
NM_001304718.2:c.301C>G
NM_000314.8:c.892C>G
More

Uncertain Significance

Met criteria codes 2
BS3_Supporting PP2
Not Met criteria codes 23
PS1 PS2 PS3 PS4 PP1 PP3 PM1 PM3 PM5 PM4 PM6 PM2 PVS1 BA1 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.892C>G (p.Q298E) 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). 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
BS3_Supporting
Mighell WT-like (0.30) results. Matreyek possibly wt-like (0.77) abundance class.
High-throughput phosphatase assay; high-confidence score in WT-like range (results 0.30). PubMed:29706350
Variant abundance measured by massively parallel sequencing; in possibly wt-like abundance class (results 0.77). PubMed:29785012
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Not Met criteria codes
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
KS changed criteria from "met" to "not met" based on Khan paper only investigating mutations with in silico models and not functional data. Khan paper (PMID, 26800850) listed variant as showing DDG values ranging from -0.05- -1.9, identified as less stable and deleterious nsSNPs using I-Mutant 2.0. This variant was not listed in the 5 found to be deleterious using combined computational tools.
PS4
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
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
ClinVar entry for c.892C>A (p.Gln298Lys) [ID: 570880]. 1 submitter, and provided algorithm information reports variant may be tolerated. Variant not found in the literature. BLOSUM = 1.
PM4
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
PM2
Global gnomAD frequency is too high to meet cut-off.
PVS1
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
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
KS changed from "met" to "not met" as there are not at least 2 cases to meet BP5. Yurgelun (2015) found variant in one indiv/1260 undergoing testing for Lynch syndrome. Indiv 1092248006 has variant and has pathogenic MLH1 mutation (dup exons 6-12)
Variant identified in 1 individual with a history of Lynch syndrome-associated cancer and/or polyps. Patient also harbored pathogenic MLH1 mutation (dup exons 6-12). PubMed:25980754
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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