Variant: NM_000314.6(PTEN):c.1171C>T (p.Pro391Ser)

CA000118

187673 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 2353f24f-8466-46ea-838d-a36a749f6a49

Approved on: 2020-03-23

Published on: 2020-03-26

HGVS expressions

NM_000314.6:c.1171C>T
NM_000314.6(PTEN):c.1171C>T (p.Pro391Ser)
NC_000010.11:g.87965431C>T
CM000672.2:g.87965431C>T
NC_000010.10:g.89725188C>T
CM000672.1:g.89725188C>T
NC_000010.9:g.89715168C>T
NG_007466.2:g.106993C>T
NM_000314.5:c.1171C>T
NM_001304717.2:c.1690C>T
NM_001304718.1:c.580C>T
NM_000314.7:c.1171C>T
NM_001304717.5:c.1690C>T
NM_001304718.2:c.580C>T
NM_000314.8:c.1171C>T
ENST00000371953.7:c.1171C>T

Uncertain Significance

• Met criteria codes: PM2 BS3 PP2

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

Expert Panel

PTEN VCEP

Criteria Specification Information

Evidence submitted by expert panel

PTEN VCEP

PTEN c.1171C>T (p.Pro391Ser) PTEN c.1171C>T (p.Pro391Ser) 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 30993208, 29785012, 29706350)

Met criteria codes

• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: Phosphatase activity, stability, pAKT, and subcellular localization similar to WT
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Not Met criteria codes

• PM4: 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
• PM5: 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
• 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
• PVS1: 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
• BP2: 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
• 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: 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
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline