Variant: NM_000314.6(PTEN):c.1061C>T (p.Pro354Leu)

CA000277

142212 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 88bdf077-351e-40ca-bbdf-1299b17f80e5

Approved on: 2019-06-25

Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.1061C>T
NM_000314.6(PTEN):c.1061C>T (p.Pro354Leu)
NC_000010.11:g.87965321C>T
CM000672.2:g.87965321C>T
NC_000010.10:g.89725078C>T
CM000672.1:g.89725078C>T
NC_000010.9:g.89715058C>T
NG_007466.2:g.106883C>T
ENST00000700029.2:c.1154C>T
ENST00000710265.1:c.*90C>T
ENST00000688158.2:n.1796C>T
ENST00000688922.2:c.*891C>T
ENST00000700021.1:c.1016C>T
ENST00000700022.1:c.*400C>T
ENST00000700023.1:n.2219C>T
ENST00000700024.1:n.2453C>T
ENST00000706954.1:c.1061C>T
ENST00000706955.1:c.*1096C>T
ENST00000686459.1:c.*647C>T
ENST00000688158.1:c.*1172C>T
ENST00000688308.1:c.1061C>T
ENST00000688922.1:c.982C>T
ENST00000693560.1:c.1580C>T
ENST00000371953.8:c.1061C>T
ENST00000371953.7:c.1061C>T
NM_000314.5:c.1061C>T
NM_001304717.2:c.1580C>T
NM_001304718.1:c.470C>T
NM_000314.7:c.1061C>T
NM_001304717.5:c.1580C>T
NM_001304718.2:c.470C>T
NM_000314.8:c.1061C>T

Uncertain Significance

• Met criteria codes: BS3_Supporting PM2 PP2

• Not Met criteria codes: BS2 BS1 BS4 BP4 BP3 BP1 BP2 BP5 BP7 PM6 PM1 PM3 PM5 PM4 PS1 PS2 PS3 PS4 BA1 PP1 PP3 PP4 PVS1

Expert Panel

PTEN VCEP

Criteria Specification Information

Evidence submitted by expert panel

PTEN VCEP

PTEN c.1061C>T (p.Pro354Leu) 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_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: KS: Matreyek results in possibly WT_like range (0.7343442462). Mighell results is WT-like (0.161537112). Suggest BS3_Supporting. Suggest BS3 for Matreyek and Mighell (FH)
• PM2: KS: Overall GnomAD allele frequency is 0.000008167. I agree (FH)
• PP2: I agree (FH)

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
• BS4: 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
• 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
• 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: KS: Our VCEP curated P354Q as VOUS. This criteria is not met at this time.
• PM4: 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: GeneDx internal data: 1 SSA dx 30s. Fam hx colon, ov, panc cancers. CC score = 0.
• BA1: 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