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

UUID: 45c8d19e-5bfc-4e2d-bc35-187033466d5d

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
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
NM_000314.8(PTEN):c.700C>T (p.Arg234Trp)

Uncertain Significance

• Met criteria codes: PM2_Supporting BS3_Supporting PP2

• Not Met criteria codes: PM5 PM3 PM1 PM4 PM6 PVS1 BS2 BS4 BS1 BP2 BP3 BP4 BP1 BP5 BP7 BA1 PS1 PS2 PS4 PS3 PP1 PP3

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Evidence submitted by expert panel

PTEN VCEP

NM_000314.8(PTEN):c.700C>T (p.Arg234Trp) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). 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: Functional studies showing no damaging effect on protein function. Score of this variant = 0.106334511 (>0, WT-like range) on high throughput phosphatase assay (PMID:29706350). Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign supporting and 2 pathogenic supporting codes get -1 + (1*2) points; total is 1 (Uncertain significance).

Met criteria codes

• PM2_Supporting: Absent in gnomAD.
• BS3_Supporting: Functional studies showing no damaging effect on protein function. Score of this variant = 0.106334511 (>0, WT-like range) on high throughput phosphatase assay (PMID:29706350).
• 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.

Not Met criteria codes

• 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
• PM3: 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
• 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
• PVS1: 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
• BS4: 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
• BP2: 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
• BP4: 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
• 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
• BA1: 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: -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.
• PS3: 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

Approved on: 2023-10-11

Published on: 2023-10-16