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.1093G>A (p.Val365Ile)

CA059160

237639 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1ebd3f87-9825-4ccc-aa05-14d1b0b78d24
Approved on: 2019-06-25
Published on: 2019-07-23

HGVS expressions

NM_000314.7:c.1093G>A
NM_000314.7(PTEN):c.1093G>A (p.Val365Ile)
NC_000010.11:g.87965353G>A
CM000672.2:g.87965353G>A
NC_000010.10:g.89725110G>A
CM000672.1:g.89725110G>A
NC_000010.9:g.89715090G>A
NG_007466.2:g.106915G>A
ENST00000700029.2:c.1186G>A
ENST00000710265.1:c.*122G>A
ENST00000688158.2:n.1828G>A
ENST00000688922.2:c.*923G>A
ENST00000700021.1:c.1048G>A
ENST00000700022.1:c.*432G>A
ENST00000700023.1:n.2251G>A
ENST00000700024.1:n.2485G>A
ENST00000706954.1:c.1093G>A
ENST00000706955.1:c.*1128G>A
ENST00000686459.1:c.*679G>A
ENST00000688158.1:c.*1204G>A
ENST00000688308.1:c.1093G>A
ENST00000688922.1:c.1014G>A
ENST00000693560.1:c.1612G>A
ENST00000371953.8:c.1093G>A
ENST00000371953.7:c.1093G>A
NM_000314.5:c.1093G>A
NM_000314.6:c.1093G>A
NM_001304717.2:c.1612G>A
NM_001304718.1:c.502G>A
NM_001304717.5:c.1612G>A
NM_001304718.2:c.502G>A
NM_000314.8:c.1093G>A
More

Uncertain Significance

Met criteria codes 3
PP2 PM2 BS3
Not Met criteria codes 23
PS1 PS2 PS3 PS4 BP4 BP3 BP1 BP2 BP5 BP7 PP1 PP3 PP4 PVS1 PM1 PM3 PM5 PM4 PM6 BA1 BS2 BS1 BS4

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.1093G>A (p.Val365Ile) 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: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (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: Missense variants with both lipid phosphatase activity AND results from a second assay appropriate to the protein domain demonstrating no statistically significant difference from wild type. (PMID 29785012, 29706350)
Met criteria codes
PP2
I agree (FH)
PM2
KS: Overall GnomAD allele frequency is 0.000008354. FH: I agree
BS3
KS: Matreyek results is WT-like (1.140914254). Mighell results is WT-like (-0.102592235). Suggest BS3_Supporting. FH: BS3 -0.1 Mighell; wt-like abundance in Matreyek (1.14)
PubMed:29785012
PubMed:29706350
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
GeneDx internal data: 2 patients with CC score = 1.
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
BP5
GeneDx internal data: 1 patient with breast and CRC dx 40s and father brain dx 50s. Harbors ATM variant.
BP7
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
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
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
PM6
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
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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