The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries.
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- Gene obtained from curated document aligns with ClinVar but not with the Allele Registry data
Variant: NM_000314.6(PTEN):c.97_99delATT (p.Ile33del)
- Curation Version - 1.0
- Curation History
- JSON LD for Version 1.0
449088 (ClinVar)
Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 18b368f7-e2f3-4e09-a961-5f209be89228
Approved on: 2023-08-04
Published on: 2023-10-19
HGVS expressions
NM_000314.6:c.97_99delATT
NM_000314.6(PTEN):c.97_99delATT (p.Ile33del)
NM_000314.8(PTEN):c.94ATT[1] (p.Ile33del)
Likely Pathogenic
Met criteria codes 4
PS3_Moderate
PP1
PM6_Strong
PM2_Supporting
Not Met criteria codes 22
BA1
BS4
BS3
BS1
BS2
BP5
BP7
BP2
BP3
BP4
BP1
PS1
PS2
PS4
PP4
PP3
PP2
PM5
PM3
PM1
PM4
PVS1
Evidence Links 0
Evidence submitted by expert panel
PTEN VCEP
PTEN c.97_99delATT (c.94ATT[1]) (p.Ile33del) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column).
PS3_Moderate: Phosphatase activity ≤ -1.11 per Mighell et al. 2018, PMID: 29706350.
PM2_Supporting: Absent in large sequenced populations (PMID 27535533).
PM6_Strong: An individual with a highly specific phenotype (Internal laboratory contributor SCV000616838.1).
PP1: Co-segregation with disease in multiple affected family members, with 5 or 6 meioses observed. (PMID 10234502 , internal laboratory contributor SCV002559099.1)
Met criteria codes
Variant scored -4.13 on high throughput lipid phosphatase assay (PMID:29706350); values below -1.11 consistent with damaging/truncation-like range. PS3 drops to PS3_M with V3 rules
Individual N6 referenced in article is one of 3 females in the family with the variant. The article does not mention the relationship between the women. The table indicates that skin, thyroid, UG, LDD, macrocephaly are reported in these individuals. Minimum 2 meioses.
Outside lab: one meiosis
Will discuss with group, see if PP1 may be allowed.
Internal laboratory contributor SCV000616838.1; patient also earns PS4_P, criteria combined with PM6 to upgrade to strong with V3 rules.
Not Met criteria codes
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
1 case with pediatric score = 6 from internal laboratory contributor SCV000616838.1. 1 phenotype specificity point = PS4_P. Criteria combined with PM6 to boost to PM6_S.
PP4
The table describing family N6 does not indicate ages, how many of the 3 females with the variant have thyroid, skin, UG, LDD or macrocephaly (the bar is half filled in for macrocephaly). It is unclear who has which combination of features. Cannot accurately calculate CC score.
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Results in an in-frame deletion causing the loss of a single isoleucine residue within the phosphatase domaine. This deletion is conserved across species.
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