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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: PTEN CSPEC Genes: [ 'PTEN' ] * Message MONDOs: MONDO:0017623 CSPEC MONDO: []
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000314.6(PTEN):c.314G>A (p.Cys105Tyr)

CA000393

142261 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: dce7b398-e447-420b-8da1-a51cbf6a8e69
Approved on: 2025-12-05
Published on: 2025-12-17

HGVS expressions

NM_000314.6:c.314G>A
NM_000314.6(PTEN):c.314G>A (p.Cys105Tyr)
NC_000010.11:g.87933073G>A
CM000672.2:g.87933073G>A
NC_000010.10:g.89692830G>A
CM000672.1:g.89692830G>A
NC_000010.9:g.89682810G>A
NG_007466.2:g.74635G>A
ENST00000700029.2:c.314G>A
ENST00000710265.1:c.314G>A
ENST00000472832.3:c.314G>A
ENST00000688158.2:n.1049G>A
ENST00000688922.2:c.*144G>A
ENST00000700021.1:c.269G>A
ENST00000700022.1:c.314G>A
ENST00000700029.1:c.148G>A
ENST00000706954.1:c.314G>A
ENST00000706955.1:c.*349G>A
ENST00000686459.1:c.314G>A
ENST00000688158.1:c.*425G>A
ENST00000688308.1:c.314G>A
ENST00000688922.1:c.235G>A
ENST00000693560.1:c.833G>A
ENST00000371953.8:c.314G>A
ENST00000371953.7:c.314G>A
ENST00000498703.1:n.140G>A
ENST00000610634.1:c.212G>A
NM_000314.5:c.314G>A
NM_001304717.2:c.833G>A
NM_001304718.1:c.-437G>A
NM_000314.7:c.314G>A
NM_001304717.5:c.833G>A
NM_001304718.2:c.-437G>A
NM_000314.8:c.314G>A
More

Pathogenic

Met criteria codes 6
PM6_Strong PS2 PP2 PP3 PM2 PS3_Moderate
Not Met criteria codes 20
BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP4 BP5 BP7 PVS1 PS4 PS1 PP1 PP4 PM3 PM1 PM4 PM5 BA1

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.314G>A (p.Cys105Tyr) 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). PM2_P: Absent in large sequenced populations (PMID 27535533). PM6_S: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history and highly specific phenotype. (internal laboratory contributor ClinVar Organization ID 26957) 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. PP3: REVEL score > 0.7 (score of this variant =0.9) PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -2.06 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor ClinVar Organization ID: 26957)
Met criteria codes
PM6_Strong
Internal case ClinVar Organization ID 26957, peds score =8. I agree (FH)
PS2
Internal case ClinVar Organization ID 26957, de novo via WES trio in pt with NDD, macrocephaly NOS, skin tags, cortical dysplasia, seizures.
PP2
I agree (FH)
PP3
REVEL = 0.9
PM2
Absent in gnomAD I agree (FH)
PS3_Moderate
Mighell = -2.06, in hypomorphic range.
Variant scored in "hypomorphic" range on high-throughput phosphatase assay. No criteria applies. PubMed:29706350
Variant disrupts interaction with LKB1 in Y2H assay. PubMed:15987703
Not Met criteria codes
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Absent in gnomAD I agree (FH)
BP2
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
BP1
I agree (FH)
BP4
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
BP7
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
PS4
GDx internal case with peds score = 8; assumed de novo case, PS4_P met but used to bump PM6 to PM6_S.
PS1
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
PP4
GDx internal case with peds score = 8. I agree (FH) Criteria moved to PS4 section.
Reported in "sporadic" BRR case with GI polyps, lipoma, penile freckling. If adult, CC score minimum = 7. If child, peds score minimum = 4. PubMed:10400993
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Could curate C105F if needed to help this get to PATH.
BA1
Absent in gnomAD I agree (FH)
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.