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.701G>A (p.Arg234Gln)

CA000551

7840 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 5fe899fa-c13c-4145-9397-0b200e380e4c
Approved on: 2018-11-28
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.701G>A
NM_000314.6(PTEN):c.701G>A (p.Arg234Gln)
NC_000010.11:g.87957919G>A
CM000672.2:g.87957919G>A
NC_000010.10:g.89717676G>A
CM000672.1:g.89717676G>A
NC_000010.9:g.89707656G>A
NG_007466.2:g.99481G>A
ENST00000700029.2:c.701G>A
ENST00000710265.1:c.701G>A
ENST00000472832.3:c.701G>A
ENST00000688158.2:n.1436G>A
ENST00000688922.2:c.*531G>A
ENST00000700021.1:c.656G>A
ENST00000700022.1:c.*40G>A
ENST00000700023.1:n.1859G>A
ENST00000700024.1:n.2093G>A
ENST00000700025.1:n.1470G>A
ENST00000700026.1:n.338G>A
ENST00000700029.1:c.535G>A
ENST00000706954.1:c.701G>A
ENST00000706955.1:c.*736G>A
ENST00000686459.1:c.*287G>A
ENST00000688158.1:c.*812G>A
ENST00000688308.1:c.701G>A
ENST00000688922.1:c.622G>A
ENST00000693560.1:c.1220G>A
ENST00000371953.8:c.701G>A
ENST00000371953.7:c.701G>A
ENST00000472832.2:c.128G>A
NM_000314.5:c.701G>A
NM_001304717.2:c.1220G>A
NM_001304718.1:c.110G>A
NM_000314.7:c.701G>A
NM_001304717.5:c.1220G>A
NM_001304718.2:c.110G>A
NM_000314.8:c.701G>A
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Uncertain Significance

Met criteria codes 2
PP2 PM2
Not Met criteria codes 24
BS1 BS4 BS3 BS2 PS1 PS2 PS3 PS4 BP5 BP7 BP4 BP3 BP1 BP2 PVS1 BA1 PP1 PP3 PP4 PM6 PM1 PM3 PM5 PM4

Evidence Links 4

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.701G>A (p.Arg234Gln) 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
I agree (FH)
PM2
I agree (FH)
Not Met criteria codes
BS1
I agree (FH)
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Need to discuss PS3_supporting with group, may not apply? Matreyek et al (no PMID yet) also describe variant as PATH in ClinVar (is actually conflicting) but with normal protein abundance. Eng lab papers also describe M3/M4 mouse with this plus 4 other PTEN missense variants; can't use for analyzing function of this variant separately. I agree with PS3_supporting for Staal et al. (FH)
“WT-like” protein abundance on high throughput assay PubMed:29785012
“WT-like” range for phosphatase activity (score -0.8, WT-like range between -1.11 and 0.89) PubMed:29706350
Variant transfected into U87MG glioma cell line (PTEN-null). Cells with mutant had 5x higher proliferation rate than WT over 2 week period and demonstrated apoptosis rate comparable to empty vector (WT had 2x rate). Mutant also had increased PKB phosphorylation. PubMed:12085208
BS2
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
Need to discuss PS3_supporting with group, may not apply? Matreyek et al (no PMID yet) also describe variant as PATH in ClinVar (is actually conflicting) but with normal protein abundance. Eng lab papers also describe M3/M4 mouse with this plus 4 other PTEN missense variants; can't use for analyzing function of this variant separately. I agree with PS3_supporting for Staal et al. (FH) Following expert panel discussion, group decided to apply no criteria based on conflicting nature of functional results.
“WT-like” protein abundance on high throughput assay PubMed:29785012
“WT-like” range for phosphatase activity (score -0.8, WT-like range between -1.11 and 0.89) PubMed:29706350
Variant transfected into U87MG glioma cell line (PTEN-null). Cells with mutant had 5x higher proliferation rate than WT over 2 week period and demonstrated apoptosis rate comparable to empty vector (WT had 2x rate). Mutant also had increased PKB phosphorylation. PubMed:12085208
PS4
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
I agree (FH)
BP2
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
BA1
I agree (FH)
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 GDx internal cases with phenotype specificity. No Ambry internal cases with phenotype specificity (FH).
Germline finding in a male pt with R frontal meningioma dx 42, L frontal low-grade glioma dx 47, this tumor turned into an anaplastic oligodendroglioma when resected at 50 yrs. This tumor recurred a few yrs later. Pt had no prev unusual med hx. Tumors also had variant and no LOH at 10q. PubMed:12085208
Germline finding in an 82yo Japanese woman with panc CA dx 82 (no LOH in tumor). Fam hx brother with gastric cancer dx 60 and sister with ovarian cancer dx 60. Workup negative for macrocephaly, skin/mucosal papillomas, thyroid/uterine/breast disease. PubMed:28755079
PM6
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
Curation History
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