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


Variant: NM_000314.4(PTEN):c.1078A>G (p.Ser360Gly)

CA000286

140777 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 7447cf4b-3a7e-436e-94f3-5cbeb5f20d28
Approved on: 2023-10-11
Published on: 2023-10-16

HGVS expressions

NM_000314.4:c.1078A>G
NM_000314.4(PTEN):c.1078A>G (p.Ser360Gly)
NC_000010.11:g.87965338A>G
CM000672.2:g.87965338A>G
NC_000010.10:g.89725095A>G
CM000672.1:g.89725095A>G
NC_000010.9:g.89715075A>G
NG_007466.2:g.106900A>G
ENST00000686459.1:c.*664A>G
ENST00000688158.1:c.*1189A>G
ENST00000688308.1:c.1078A>G
ENST00000688922.1:c.999A>G
ENST00000693560.1:c.1597A>G
ENST00000371953.8:c.1078A>G
ENST00000371953.7:c.1078A>G
NM_000314.5:c.1078A>G
NM_000314.6:c.1078A>G
NM_001304717.2:c.1597A>G
NM_001304718.1:c.487A>G
NM_000314.7:c.1078A>G
NM_001304717.5:c.1597A>G
NM_001304718.2:c.487A>G
NM_000314.8:c.1078A>G
NM_000314.8(PTEN):c.1078A>G (p.Ser360Gly)
More

Likely Benign

Met criteria codes 3
PP2 BS1_Supporting BP4
Not Met criteria codes 22
PP4 PP1 PP3 PM3 PM1 PM5 PM4 PM6 PS4 PS2 PS3 PS1 BA1 PVS1 BP2 BP1 BP3 BP5 BP7 BS2 BS4 BS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
NM_000314.8(PTEN):c.1078A>G (p.Ser360Gly) meets criteria to be classified as likely benign 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). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. BS1_P: To be applied for variants with filtering allele frequency of 0.0000043 up to 0.000043 (0.00043% up to 0.0043%) in gnomAD. Popmax FAF of this variant=0.00001171. BP4: REVEL score < 0.5 (score of this variant=0.441). Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 2 benign supporting and 1 pathogenic supporting codes get (-1*2) + 1 points; total is –1 (likely benign).
Met criteria codes
PP2
PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
BS1_Supporting
To be applied for variants with filtering allele frequency of 0.0000043 up to 0.000043 (0.00043% up to 0.0043%) in gnomAD. Popmax FAF of this variant=0.00001171.
BP4
REVEL score < 0.5 (score=0.441)
Not Met criteria codes
PP4
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
PP3
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
KS: ClinVar/Invitae entry for Ser360Thr, however no cases reported in the literature. Ser360Thr will likely not meet likely pathogenic so not necessary to work up now, but may want to revisit in the future.
PM4
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
PS4
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
PS3
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
BP1
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
BP5
GeneDx internal data: 48yo F with ovarian cancer dx 47, small bowel GIST dx 47, clinical dx NF1 (details not provided) and found to harbor NF1 variant.
BP7
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Mighell: -0.28150236 in Column G (TURE in Column I)
Curation History
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