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.507delC (p.Ser170Valfs)

CA000490

7843 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: cda272e6-a64d-4303-8640-80c038c51db1
Approved on: 2018-07-25
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.507delC
NM_000314.6(PTEN):c.507delC (p.Ser170Valfs)
NC_000010.11:g.87952132del
CM000672.2:g.87952132del
NC_000010.10:g.89711889del
CM000672.1:g.89711889del
NC_000010.9:g.89701869del
NG_007466.2:g.93694del
NM_000314.5:c.507del
NM_000314.6:c.507del
NM_001304717.2:c.1026del
NM_001304718.1:c.-85del
NM_000314.7:c.507del
NM_001304717.5:c.1026del
NM_001304718.2:c.-85del
ENST00000371953.7:c.507del

Pathogenic

Met criteria codes 4
PVS1 PS4 PM2 PM6
Not Met criteria codes 18
BS2 BS1 BS3 BS4 BP4 BP2 BP7 BP5 PS1 PS3 PS2 BA1 PP3 PP2 PP1 PM5 PM4 PM1

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.507delC (p.Ser170Valfs) 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). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 12471211) PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 12471211)
Met criteria codes
PVS1
Agreed - predicted to cause premature truncation resulting in a stop codon (TAA) 38 nucleotides downstream within exon 6. MP
PS4
Smith 2002 PMID 12471211
Proband is 15m M with features of Proteus syndrome (epidermal nevus, capillary venous malformation, lipoma, OFC big at birth). Over time: more lipomas, R leg overgrowth, multiple GI lymphoid aggregates, lack of OFC growth but still relative macrocephaly (OFC 50-98%, ht 1-3%, wt 50%). No ID/DD. Peds score = 5 based on OFC at birth and relative high OFC later in life, PS4_supporting approved on EP review. PubMed:12471211
PM2
Variant absent from population databases. Agreed, not found in gnomAD (MP)
PM6
Reported as confirmed de novo in Smith paper (MP).
Mother and father tested for proband's PTEN mutation and were negative. No note of if maternity and paternity were confirmed. Mother has history of fundic glandular polyps in stomach and hyperplastic distal rectal polyps. Maternal family history of unilateral breast cancer. No family history of macrocephaly or dermatologic findings related to Cowden syndrome. PubMed:12471211
Mutation listed in Table 3 as a mutation identified in a patient with Proteus syndrome. PubMed:12938083
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Variant absent from population databases. Agreed, not found in gnomAD (MP)
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
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
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
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
Mother and father tested for proband's PTEN mutation and were negative (clearly stated in paper, but no sequencing shown - MP). No note of if maternity and paternity were confirmed. Mother has history of fundic glandular polyps in stomach and hyperplastic distal rectal polyps. Maternal family history of unilateral breast cancer (GM, GGM, 5 MA's, did not have genetic testing for BRCA etc - MP). No family history of macrocephaly or dermatologic findings related to Cowden syndrome. (agreed, MP)
Mother and father tested for proband's PTEN mutation and were negative. No note of if maternity and paternity were confirmed. Mother has history of fundic glandular polyps in stomach and hyperplastic distal rectal polyps. Maternal family history of unilateral breast cancer. No family history of macrocephaly or dermatologic findings related to Cowden syndrome. PubMed:12471211
Mutation listed in Table 3 as a mutation identified in a patient with Proteus syndrome. PubMed:12938083
BA1
Variant absent from population databases. Agreed, not found in gnomAD (MP)
PP3
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
PP1
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Variant not in specified residues for applying criteria.
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