Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000314.6(PTEN):c.-1195_-1184delAAGCCGCAGCAA

CA163819

189433 (ClinVar)

Gene: KLLN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a4de2dba-9fd0-4e69-a9e5-2e6d4ec56af5

HGVS expressions

NM_000314.6(PTEN):c.-1195_-1184delAAGCCGCAGCAA

NC_000010.11:g.87863274_87863285del

CM000672.2:g.87863274_87863285del

NC_000010.10:g.89623031_89623042del

CM000672.1:g.89623031_89623042del

NC_000010.9:g.89613011_89613022del

NG_007466.2:g.4837_4848del

NG_033079.1:g.5157_5168del

NM_001126049.1:c.-794_-783del

ENST00000371953.7:c.-1196_-1185del

ENST00000445946.3:c.-794_-783del

Likely Benign

BS4_Supporting BP5

PS4 PS2 PS3 PS1 BP4 BP2 BP7 BA1 PP2 PP3 PP1 PM4 PM1 PM5 PVS1 PM2 PM6 BS2 BS1 BS3

Evidence Links 6

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.-1195del12 (NC_000010.10:g.89623031_89623042delAAGCCGCAGCAA) meets criteria to be classified as likely benign 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). BS4_P: Lack of segregation in affected members of one family. (Internal laboratory contributor SCV SCV000222146.7) BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributors SCV000222146.7, SCV000183826.5)

BS4_Supporting

Consider BS4_P. GDx internal data: identified in teenage F with macrocephaly. Also present in teenage sister with normal OFC, no PHTS cutaneous features. NEGATIVE in teenage sister with macrocephaly (OFC 62.2cm), overgrowth, early puberty, no PHTS-related skin findings. Mother, 40s, also positive for variant, no clinical info.

BP5

Multiple co-occurrences from clinical laboratory contributors: SCV000222146.7, SCV000183826.5 - BRCA2, MSH6, MEN1, MLH1

PS4

Identified in a cohort of premenopausal breast cancer patients who underwent oopherectomy PubMed:28821472

Variant listed in Table S2 as a pathogenic mutation identified in 2 individuals. A 58.2-year-old and a 59.1-year-old. Participants met relaxed ICC operational criteria per subjects and methods section. No additional patient specific information reported. PubMed:21194675

Variant listed as identified in this study in Supplementary Table 4. No additional patient specific information reported. Patients met full or relaxed criteria for Cowden syndrome per methods section. PubMed:25669429

Identified in 2 females. A 35-year-old, non-hispanic white, non-Ashkenazi Jewish, no personal history of cancer, family history of gynecologic and prostate cancers (CC score = 0). A 57-year-old, non-hispanic white, non-Ashkenazi Jewish, personal history of endometrial cancer, family history of other cancers (CC Score = 1. PubMed:28495237

Identified in 2 individuals. The first, a 53 year old female, reported to have a history of breast at 51 and thyroid cancer at 42. The second, a 57 year old female, with a history of breast cancer at 52 and no history of thyroid cancer. PubMed:21532617

Identified in a 19 year old Hispanic male jejunum carpeting of hamartomous polyps containing foveolar and gastric-type tissue with arborizing streaks of smooth muscle and minimal inflammation. NGS panel completed [APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53). Only finding was PTEN c.-1196_-1185del12. OFC 62cm but 6'2" and 225lbs, no derm/other PHTS findings. CC score = 26, 0.5 phenotype specificity points. PubMed:28157521

PS2