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.700C>T (p.Arg234Trp)

CA000183

184844 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 45c8d19e-5bfc-4e2d-bc35-187033466d5d
Approved on: 2019-03-05
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.700C>T
NM_000314.6(PTEN):c.700C>T (p.Arg234Trp)
NC_000010.11:g.87957918C>T
CM000672.2:g.87957918C>T
NC_000010.10:g.89717675C>T
CM000672.1:g.89717675C>T
NC_000010.9:g.89707655C>T
NG_007466.2:g.99480C>T
ENST00000700029.2:c.700C>T
ENST00000710265.1:c.700C>T
ENST00000472832.3:c.700C>T
ENST00000688158.2:n.1435C>T
ENST00000688922.2:c.*530C>T
ENST00000700021.1:c.655C>T
ENST00000700022.1:c.*39C>T
ENST00000700023.1:n.1858C>T
ENST00000700024.1:n.2092C>T
ENST00000700025.1:n.1469C>T
ENST00000700026.1:n.337C>T
ENST00000700029.1:c.534C>T
ENST00000706954.1:c.700C>T
ENST00000706955.1:c.*735C>T
ENST00000686459.1:c.*286C>T
ENST00000688158.1:c.*811C>T
ENST00000688308.1:c.700C>T
ENST00000688922.1:c.621C>T
ENST00000693560.1:c.1219C>T
ENST00000371953.8:c.700C>T
ENST00000371953.7:c.700C>T
ENST00000472832.2:c.127C>T
NM_000314.5:c.700C>T
NM_001304717.2:c.1219C>T
NM_001304718.1:c.109C>T
NM_000314.7:c.700C>T
NM_001304717.5:c.1219C>T
NM_001304718.2:c.109C>T
NM_000314.8:c.700C>T
More

Uncertain Significance

Met criteria codes 3
BS3_Supporting PP2 PM2
Not Met criteria codes 22
BA1 BS1 BS4 BS2 BP5 BP7 BP4 BP3 BP1 BP2 PVS1 PS1 PS2 PS3 PS4 PP1 PP3 PM1 PM3 PM5 PM4 PM6

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.700C>T (p.R234W) 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
BS3_Supporting
variant scored 0.106 on high throughput lipid phosphatase assay; values between -1.11 and 0.89 are consistent with WT-like range.
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Not found in gnomAD.
Not Met criteria codes
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
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
PVS1
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
-Internal GDX cases: one female patient in her 60's - 3 breast primaries and fam hx of breast ca = CC score of 1. Second case of male in 60's with colon polyps (20+) and 3 fundic gland polyps. Brother with 14 polyps. CC score is 6. CC score to low to qualify for PS4. -Other internal cases CC score = 1-2.
Variant found in at least 3 breast cancer patients. No additional patient specific information reported. CC score = 1. PubMed:30039884
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.700C>G (p.Arg234Gly) [ID: 482337)]: 1 submitter with no additional information in the entry and variant not found in the literature. ClinVar entry for c.701G>A (p.Arg234Gln) [ID: 7840]: 4 submitters and variant reported in 3 patients in the literature, so possible that this variant should be reviewed? BLOSUM = -2
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
Curation History
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