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_000314.7(PTEN):c.830C>G (p.Thr277Arg)

CA377485523

428268 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 579af9bf-2984-45d2-8e0a-bd0802a7860b
Approved on: 2020-03-23
Published on: 2020-03-26

HGVS expressions

NM_000314.7:c.830C>G
NM_000314.7(PTEN):c.830C>G (p.Thr277Arg)
NC_000010.11:g.87960922C>G
CM000672.2:g.87960922C>G
NC_000010.10:g.89720679C>G
CM000672.1:g.89720679C>G
NC_000010.9:g.89710659C>G
NG_007466.2:g.102484C>G
NM_000314.5:c.830C>G
NM_000314.6:c.830C>G
NM_001304717.2:c.1349C>G
NM_001304718.1:c.239C>G
NM_001304717.5:c.1349C>G
NM_001304718.2:c.239C>G
NM_000314.8:c.830C>G
ENST00000371953.7:c.830C>G
ENST00000472832.2:n.257C>G
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Likely Pathogenic

Met criteria codes 4
PS3 PP2 PM2 PP1_Moderate
Not Met criteria codes 18
BS2 BS1 BS3 BS4 BP5 BP7 BP4 BP2 PS1 PS2 PS4 PP3 BA1 PM4 PM1 PM5 PVS1 PM6

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.830C>G (p.Thr277Arg) meets criteria to be classified as likely 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). PS3: Phosphatase activity <50% of wild type (PMID 29706350) PM2: Absent in large sequenced populations PP1_M: Co-segregation with disease in multiple affected family members, with 5 or 6 meioses observed. (PMID 23335809) 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
PS3
Mighell et al. 2018 High-throughput functional assay testing PTEN lipid phosphatase activity. T277R had a score of -3.839319668 and was 'TRUE', which means this variant had truncation-like function.
High-throughput functional assay testing PTEN lipid phosphatase activity. T277R had a score of -3.839319668 and was 'TRUE', which means this variant had truncation-like function. PubMed:29706350
PP2
Missense
PM2
Not present in gnomAD (coverage >30x).
PP1_Moderate
Pedigree provided by Dr. Longy confirming 5 meioses.
PubMed:23335809
Not Met criteria codes
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
PubMed:23335809
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
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
PS4
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
BA1
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
PVS1
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
Curation History
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