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]
  • See Evidence submitted by expert panel for details.

Variant: NM_000314.6(PTEN):c.195C>G (p.Tyr65Ter)

CA10582757

237643 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 994ade45-e2c0-40c5-9bb6-a646666f386c
Approved on: 2019-03-05
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.195C>G
NM_000314.6(PTEN):c.195C>G (p.Tyr65Ter)
NC_000010.11:g.87925543C>G
CM000672.2:g.87925543C>G
NC_000010.10:g.89685300C>G
CM000672.1:g.89685300C>G
NC_000010.9:g.89675280C>G
NG_007466.2:g.67105C>G
NM_000314.5:c.195C>G
NM_001304717.2:c.714C>G
NM_001304718.1:c.-541-5503C>G
NM_000314.7:c.195C>G
NM_001304717.5:c.714C>G
NM_001304718.2:c.-541-5503C>G
ENST00000371953.7:c.195C>G
ENST00000498703.1:n.21C>G
ENST00000610634.1:c.93C>G
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Pathogenic

Met criteria codes 3
PM2 PVS1 PS4_Supporting
Not Met criteria codes 18
PS1 PS2 BA1 PM4 PM5 PM1 PM6 PP2 PP3 PP1 BS1 BS3 BS4 BS2 BP7 BP5 BP4 BP2

Evidence Links 5

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.195C>G (p.Y65X) 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 23335809)
Met criteria codes
PM2
KS: Absent in gnomAD. MP agrees.
PVS1
KS: Premature termination codon (nonsense) subject to NMD. MP agrees.
PS4_Supporting
Bubien 2013
Variant listed in Table S2 as identified in a proband who is age 31.1. Authors report that probands met relaxed International Cowden Consortium operational criteria for CS. PubMed:21194675
Case 190 with BRRS, autism, macrocephaly, and hyperactivity. Child CC score = 4. PubMed:28454995
Per K. Sesock: Patient 4 with CS. Present: mucocutaneous lesions, facial papules, oral mucosal papillomatosis, acral keratoses, speckled penis, GI polyps, benign thyroid. OFC = not done. CC score = about 17. Per J. Mester: per personal correspondence from Dr. Longy (corresponding author), pt was adult with goiter at age 20, left hemicolectomy at 33 y for polyposis coli with hamartomatous polyps, mild mental retardation, oral papillomatosis, cutaneous fibroma, acral keratosis, genital lentigines, meningioma. Recalculated CC score = 34 based on updated polyp information, PS4_P applies. PubMed:23335809
Not Met criteria codes
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
BA1
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
PM5
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
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
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
PubMed:29785012
PubMed:29706350
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
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
Curation History
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