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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000314.6(PTEN):c.512dup (p.Arg172Glufs)

CA645369422

428206 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: df053db0-9ad9-48ee-aea1-550cda8b3586
Approved on: 2019-03-05
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.512dup
NM_000314.6(PTEN):c.512dup (p.Arg172Glufs)
NC_000010.11:g.87952137dup
CM000672.2:g.87952137dup
NC_000010.10:g.89711894dup
CM000672.1:g.89711894dup
NC_000010.9:g.89701874dup
NG_007466.2:g.93699dup
NM_000314.5:c.512dup
NM_001304717.2:c.1031dup
NM_001304718.1:c.-80dup
NM_000314.7:c.512dup
NM_001304717.5:c.1031dup
NM_001304718.2:c.-80dup
ENST00000371953.7:c.512dup

Pathogenic

Met criteria codes 3
PS4_Supporting PVS1 PM2
Not Met criteria codes 19
BP7 BP5 BP4 BP2 PS1 PS3 PS2 BA1 PP2 PP3 PP1 PM5 PM4 PM1 PM6 BS1 BS3 BS4 BS2

Evidence Links 10

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.512dup (p.R172Efs) meets criteria to be classified as pathogenic 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5’ to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations (PMID 27535533). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 17526801)
Met criteria codes
PS4_Supporting
Per K. Sesock: At least 2 patients (please see notes below). A patient with CC score = at least 10, and a pediatric patient with a peds score = 11. Per J. Mester: agree PS4_supporting; strongly suspect pt reported in CCF and Boston publications is the same individual.
Reviewed by K. Sesock: Patient 16: Variant referred to as c.513insA. Female, 8.5 years at diagnosis, GI polyps. Maternal uncle with PTEN mutation. 7 years at first PHTS symptom of multiple GI polyps. OFC = >97%. None of the following present: mental retardation/global developmental delay, pervasive developmental disorder. Normal brain MRI performed for the indication of macrocephaly, large anterior fontanelle at 23 months. Also, diagnosed with non-medullary thyroid cancer, solitary thyroid nodule, genitourinary malformation, lipomas. Peds score = 11. (JM agree 1 phenotype specificity point) PubMed:17526801
Variant referred to as c.514dupA in Table 2, and 4 patients with variant are reported. No additional patient specific information reported. PubMed:21659347
Institution overlap (no author overlap) and patient overlap with PMID 17526801. Authors further characterize thyroid findings to include 2.0-cm nodule in left thyroid lobe, thyroidectomy revealed multiple follicular adenomas with a papillary microcarcinoma in the largest adenoma PubMed:20962022
Institution overlap, author overlap, and likely patient overlap with PMID 20600018. Patient age of 19.4 is listed in Table S2, however no additional patient specific information reported. PubMed:21194675
Author overlap and likely patient overlap with PMIDs 21194675, 20600018. PubMed:21956414
Author overlap and likely patient overlap with PMIDs 21194675, 20600018, 21956414. PubMed:22261759
Patient 3349: Multiple hamartomas. No additional patient specific information reported. CC score = 10 (at least) PubMed:20600018
Author overlap and likely patient overlap with PMIDs 21194675, 20600018, 21956414, 22261759. Variant listed identified in this study in Supplementary Table 4. PubMed:25669429
Likely patient overlap with PMIDs 17526801, 20962022. PubMed:21190448
Author overlap and possible patient overlap with PMIDs 21194675, 20600018, 21956414, 22261759, 25669429. This study reports a 21-year-old female with Cowden syndrome and lymphoid hyperplasia. This could be the same patient as the 19.4-year-old patient reported in PMID 21194675, however there is limited information to confirm if this is the same patient or not. PubMed:27477328
PVS1
Premature termination codon (frameshift) subject to nonsense-mediated decay. (JM agree)
PM2
Absent in gnomAD. (JM agree)
Not Met criteria codes
BP7
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
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
PS1
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
PS2
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
PP2
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
Patient from PMID 17526801 has a maternal uncle with PTEN mutation, however not enough meioses to meet criteria.
PM5
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
PM1
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
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
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
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